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A Special Issue of Journal of Clinical Medicine (ISSN 2077-0383) belonging to the section "Clinical Neurology".

Deadline for manuscript submissions: 20 October 2026 | Viewed by 16885

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Dr. Marta Iacobucci

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Interventional and Diagnostic Neuroradiology, University Hospital Policlinico Umberto I of Rome, Sapienza University of Rome, Rome, Italy
Interests: acute ischemic stroke; neuroprotection; reperfusion injury

Special Issue Information

Dear Colleagues,

The landscape of acute ischemic stroke (AIS) management has undergone a paradigm shift in recent years, largely due to the advent of advanced neurointerventional techniques and the refinement of pharmacological treatments. Despite significant progress in the acute phase, challenges persist in maximizing patient outcomes, expanding treatment eligibility, and improving recovery for those affected by this devastating condition. As a result, current research efforts are increasingly focused on innovative techniques and therapeutic strategies aimed at both the acute treatment and long-term recovery of AIS patients. The next frontier lies in the integration of novel endovascular techniques, molecular therapies, and personalized medicine approaches. Expanding the treatment window for thrombectomy, refining neuroprotective drugs, advancing stem cell therapies, and harnessing the power of AI and predictive models represent exciting opportunities for the future of stroke care. As these research efforts progress, they hold the potential not only to improve the acute management of ischemic stroke but also to reshape the landscape of recovery, offering hope for more effective treatments and better outcomes for stroke patients globally.

Therefore, in this Special Issue, the authors are invited to submit papers related to “Acute Ischemic Stroke Management Strategies” exploring new perspective of therapy in acute ischemic stroke.

Dr. Marta Iacobucci
Guest Editor

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Keywords

mechanical thrombectomy
leptomeningeal collateral circulation
neuroprotection
reperfusion injury
ischemic penumbra

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Published Papers (9 papers)

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Research

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13 pages, 1003 KB

Open AccessArticle

Impact of Anesthesia Modality on Clinical Outcomes in Anterior Circulation Stroke Patients Undergoing Mechanical Thrombectomy: A Retrospective Propensity Score-Matched Analysis

by Mustafa Çetiner, Ayşe Nur Akca, Gönül Akdağ, Buse Kozlu, İrem Yıldırım, Abdulhamit Şehid Kılınç, Esma Aşık, Burcu Kaplan, Fahri Şen and Nurullah Can Aydoğdu

J. Clin. Med. 2026, 15(13), 4916; https://doi.org/10.3390/jcm15134916 - 24 Jun 2026

Viewed by 415

Abstract

Background/Objectives: The type of anesthesia in patients with acute stroke is still controversial. This study aimed to investigate the effect of anesthesia management on clinical outcomes in patients with anterior circulation stroke undergoing mechanical thrombectomy. Methods: In this observational, retrospective study, patients with acute anterior circulation stroke who underwent mechanical thrombectomy between January 2021 and March 2025 were retrospectively reviewed. Patients were divided into groups according to the type of anesthesia administered. Functional independence was assessed at 90 days using the modified Rankin Scale. A TICI of 2b or higher was defined as successful reperfusion. In the conscious sedation (CS) and general anesthesia (GA) groups, patients were analyzed based on baseline characteristics and clinical outcomes using Propensity Score Matching. Results: In the propensity score-matched cohort, there was no significant difference between the two groups in terms of good functional outcome (mRS ≤ 2) (p = 0.82). When compared by successful reperfusion rate (TICI 2b or higher), it was significantly higher in the GA group (p = 0.01). Conclusions: In this study, the use of GA resulted in higher recanalization rates in patients with anterior circulation stroke undergoing mechanical thrombectomy. However, no differences were observed between the GA and CS groups in terms of functional outcomes, mortality, or peri-procedural/post-procedural complications. Full article

(This article belongs to the Special Issue Acute Ischemic Stroke Management Strategies)

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26 pages, 3624 KB

Open AccessArticle

Construction and Validation of a 90-Day Mortality Risk Prediction Model Based on Interpretable Machine Learning for Acute Ischemic Stroke Patients Undergoing Mechanical Thrombectomy

by Qian Jiang, Rui Wang, Yueyue He, Lingxiao He, Nan Wen, Jianyu Peng, Junli Zhang and Ling Feng

J. Clin. Med. 2026, 15(12), 4702; https://doi.org/10.3390/jcm15124702 - 17 Jun 2026

Viewed by 420

Abstract

Background/Objectives: The accurate prediction of postprocedural mortality is critical for clinical decision-making; however, research on mortality risk models for patients undergoing mechanical thrombectomy remains limited. This study aimed to develop and validate machine learning models for predicting 90-day post-mechanical thrombectomy mortality. Methods: A retrospective-prospective cohort study involving 699 retrospective patients (January 2019–December 2022) and 274 prospective patients (January 2023–June 2024) from a single institution in Sichuan was conducted. The primary outcome was all-cause mortality within 90 days, ascertained via telephone follow-up. Predictors were identified using univariate analysis and LASSO regression. Eight predictive models were developed and evaluated using existing machine learning methods via 10-fold cross-validation. Model performance was assessed through discrimination, calibration, decision curve analysis, and interpretability via Shapley additive explanations. Results: The final dataset included 593 patients in the modeling set and 247 in the validation set. The 90-day mortality rates were 25.6% and 32.0%, respectively. Key predictors included age, hyperlipidemia, atrial fibrillation, pre-stroke statin use, antiplatelet/anticoagulant therapy within 48 h of onset, dysphagia, D-dimer levels, and activities of daily living scores. Logistic regression demonstrated superior performance in the modeling cohort (AUC = 0.87), whereas the multilayer perceptron model exhibited the greatest efficacy in the validation cohort (AUC = 0.77). Conclusions: Machine learning algorithms can accurately predict 90-day mortality among patients undergoing mechanical thrombectomy. The multilayer perceptron model demonstrated robust validation performance and offers a potential tool for personalized risk assessment and optimization of clinical decision-making. Full article

(This article belongs to the Special Issue Acute Ischemic Stroke Management Strategies)

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13 pages, 2158 KB

Open AccessArticle

Relationship Between Routine Preoperative Chest CT-Based Cardiac Parameters and Recanalization After Mechanical Thrombectomy in Patients with Acute Ischemic Stroke

by Weizhi Xia, Yingbao Huang, Qi Chen, Xue Wang, Zhihan Yan and Wenru Zhang

J. Clin. Med. 2026, 15(12), 4446; https://doi.org/10.3390/jcm15124446 - 9 Jun 2026

Viewed by 385

Abstract

Purpose: Acute ischemic stroke (AIS) is the most prevalent stroke subtype. Given the brain–heart interaction, this study investigated the association between cardiac parameters on admission routine preoperative chest CT and recanalization following thrombectomy in AIS patients. Method: We retrospectively analyzed 215 AIS patients (August 2018–June 2022) who underwent admission of none contrast chest computed tomography (NCCT) and thrombectomy within 24 h. Successful recanalization was defined as modified Treatment in Cerebral Ischemia (mTICI) score 2b-3. Multivariable logistic regression identified independent predictors. A nomogram was developed and validated using ROC, calibration, and decision curve analyses. Result: The cohort had a median age of 72 years; 63.7% were male. Hypertension (65.1%), atrial fibrillation (25.1%), and pleural effusion (56.3%) were prevalent. Successful recanalization occurred in 172 patients (80%). Independent predictors included mean arterial pressure (OR: 1.022, CI: 1.003–1.041, p = 0.025), left pulmonary artery diameter (OR: 0.838, CI: 0.733–0.958, p = 0.010), RV/A ratio (standardized) (OR:1.908, CI: 1.293–2.817, p = 0.001), septal angle (OR: 1.055, CI: 1.018–1.094, p = 0.004), and intraventricular septal angle (OR: 0.973, CI: 0.952–0.995, p = 0.015). The model achieved an AUC of 0.774 (p < 0.001) with strong calibration and net benefit. Conclusions: Cardiac parameters on routine preoperative chest CT correlate with recanalization following thrombectomy in AIS patients. The developed nomogram offers a reliable tool for clinical risk stratification. Full article

(This article belongs to the Special Issue Acute Ischemic Stroke Management Strategies)

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15 pages, 736 KB

Open AccessArticle

Low Fibrinogen Levels Are Associated with an Increased Risk of Parenchymal Hematoma in Ischemic Stroke Treated with Intravenous Thrombolysis

by Libor Šimůnek, Veronika Kunešová, Lucie Burešová, Viktor Weiss, René Jura, Petr Geier, Petra Reková, Daniel Václavík, Martin Šrámek, Robert Mikulík and Roman Herzig

J. Clin. Med. 2026, 15(5), 1691; https://doi.org/10.3390/jcm15051691 - 24 Feb 2026

Viewed by 915

Abstract

Background: Intravenous thrombolysis (IVT), used in acute ischemic stroke (AIS), may be complicated by the development of intracranial hemorrhage. The role of fibrinogen levels, including their decrease, as a possible predictor of intracranial hemorrhage, has not yet been fully clarified. We aimed to evaluate the association between fibrinogen levels and their decrease 6 and 24 h after IVT and the risk of parenchymal hematoma (PH), as the clinically most significant type of intracranial hemorrhage. Methods: In an observational, nationwide, multicenter study, data from adult patients who underwent IVT for AIS from the Registry of Stroke Care Quality (RES-Q) in the Czech Republic (2019–2021) were analyzed. An association between fibrinogen levels and their decrease 6 and 24 h after IVT and the risk of PH was assessed. Results: We analyzed a set of 27 patients with PH (13 males; median age 78.0 years) and a control group (CG) of 97 patients without intracranial hemorrhage (58 males; median age 78.0 years). Fibrinogen levels 6 h after IVT (median 1.93 [PH] vs. 2.57 [CG] g/L, p = 0.012) and the ratio of baseline fibrinogen to fibrinogen 6 h after IVT (median 1.78 [PH] vs. 1.26 [CG]; p = 0.008) were associated with the development of PH. The optimal cut-off value of fibrinogen 6 h after IVT for predicting PH was <2.0 g/L. Conclusions: Fibrinogen levels 6 h after IVT and the ratio of baseline fibrinogen to fibrinogen 6 h after IVT are associated with an increased risk of PH in patients with acute ischemic stroke treated with IVT. Full article

(This article belongs to the Special Issue Acute Ischemic Stroke Management Strategies)

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15 pages, 875 KB

Open AccessCommunication

Thrombus Composition and the Evolving Role of Tenecteplase in Acute Ischemic Stroke

by Senta Frol and Matija Zupan

J. Clin. Med. 2025, 14(24), 8675; https://doi.org/10.3390/jcm14248675 - 7 Dec 2025

Cited by 3 | Viewed by 1289

Abstract

Acute ischemic stroke (AIS) is a leading cause of disability and death worldwide, requiring rapid reperfusion to minimize damage. Current treatments, including intravenous thrombolysis (IVT) with alteplase (rt-PA) and mechanical thrombectomy (MT), face limitations such as thrombolysis resistance, dosing complexity, and reduced efficacy in large vessel occlusions (LVOs) or fibrin-rich clots. Tenecteplase (TNK), a bioengineered thrombolytic agent with superior pharmacokinetics, simplified administration, and higher fibrin specificity, offers promising advantages over rt-PA, including potential synergy with MT and efficacy against resistant thrombi. Direct oral anticoagulants (DOACs) further complicate AIS management, but evidence suggests that DOAC-treated patients may experience better thrombolysis outcomes due to distinct thrombus characteristics. Advances in imaging now enable precise visualization of vessel occlusion and treatment effects, opening opportunities to refine therapies. Combination approaches targeting fibrin thrombus components may enhance thrombolysis and improve outcomes in resistant cases. Future research should explore TNK’s role in intra-arterial (IA) applications, combination therapies, and its interaction with MT to optimize reperfusion strategies. TNK’s simplified use and promising efficacy position it as a potential breakthrough in AIS management, with the potential to improve functional recovery and reduce treatment complexity. Full article

(This article belongs to the Special Issue Acute Ischemic Stroke Management Strategies)

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11 pages, 1529 KB

Open AccessArticle

Evaluation of Intracranial Arteriovenous Malformations Using Ischemic Stroke Color-Coded Maps Software, a New Rapid Post-Processing Tool in CT Angiography

by Francesco D’Argento, Tommaso Verdolotti, Rosa D’Abronzo, Davide De Leoni, Emanuele Ferravante, Francesco Arbia, Marta Iacobucci, Simona Gaudino, Matteo Mancino, Chiara Schiarelli, Giuseppe Garignano and Alessandro Pedicelli

J. Clin. Med. 2025, 14(16), 5833; https://doi.org/10.3390/jcm14165833 - 18 Aug 2025

Viewed by 7124

Abstract

Background/Objectives: In patients with intracranial arteriovenous malformation (AVM), the first diagnostic analysis is often performed in emergency conditions by Computed Tomography (CT) and multiphase CT angiography (CTA). Nevertheless, once ruptured, an AVM might be hardly recognized by an inexperienced neuroradiologist, due to the presence of hematoma or to the destructuring of the lesion. The aim of our study is to outline the utility of color-coded maps derived from multiphase CT angiography in the assessment of cerebral AVMs, evaluating inter-observer agreement between radiologists with different years’ experience and comparing the results with the gold standard, angiography. Methods: The color-coded maps were obtained retrospectively by multiphase CT angiography on a workstation using FastStroke software ColorViz (GE Healthcare, Milwaukee, WI, USA). The color-coded maps were evaluated, independently, by two neuroradiologists, and inter-observer agreement was evaluated. Finally, the AVM’s features (arterial feeders, nidus type, venous drainage type) obtained with color-coded maps were compared with angiographic analysis. The Ethical Committee for Research in Medical Imaging approved this study (Institutional Review Board number 6467). Informed consent was obtained for every patient. Results: A total of 26 patients with intracranial hemorrhage and arteriovenous malformation underwent multiphase CT angiography and were analyzed. Our statistical analysis showed the reproducibility of the color-coded maps and agreement with the angiographic findings, especially in the evaluation of venous drainage type. Conclusions: The ColorViz color-coded maps have proved to be an effective tool in the identification and assessment of AVMs, providing rapid and clear information on intracranial vascular dynamics, even for inexperienced radiologists. Full article

(This article belongs to the Special Issue Acute Ischemic Stroke Management Strategies)

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Review

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23 pages, 1128 KB

Open AccessReview

Beyond Recanalization: A Mechanistic and Procedural Framework for Adjunct Pharmacologic Therapy During Mechanical Thrombectomy

by Saniyah Shaikh, Touleen T. Raslan, Affaf Tanweer, Zainab Nasir, Hibba Siraj, Thaabit Raziq, Umaima Shoukat, Volodymyr Mavrych, Olena Bolgova and Ahmed Yaqinuddin

J. Clin. Med. 2026, 15(17), 6681; https://doi.org/10.3390/jcm15176681 - 28 Aug 2026

Viewed by 489

Abstract

Endovascular thrombectomy [EVT] has revolutionized acute ischemic stroke care by restoring macrovascular reperfusion in large vessel occlusion; however, a persistent “reperfusion–outcome gap” remains, leaving nearly half of successfully recanalized patients without functional independence. This review aims to bridge this translational gap by establishing a mechanistic and procedural framework for adjunctive pharmacotherapy designed to target the microvascular, thromboinflammatory, and reperfusion-related injuries left unaddressed by purely mechanical models. Synthesis of recent literature reveals that futile recanalization is driven by three distinct anatomical and biological bottlenecks: distal microembolization, microcirculatory no-reflow, and ischemia–reperfusion injury. Furthermore, the inconsistency of clinical trial results reflects a critical precision deficit, including dilution of treatment effects across heterogeneous reperfusion grades, inadequate stroke etiology stratification, delayed pharmacologic intervention relative to evolving microvascular injury, and reliance on functional endpoints that inadequately capture tissue-level reperfusion. To address these limitations, this review outlines a tri-axial clinical decision framework integrating reperfusion status, stroke etiology and hemorrhagic risk, which maps specific patient phenotypes, such as incomplete macrovascular reperfusion or underlying intracranial atherosclerotic disease, to targeted pharmacologic strategies including microcatheter-directed intra-arterial thrombolytics and glycoprotein IIb/IIIa inhibitors. The review further argues that future progress will require imaging-guided identification of residual hypoperfusion, mechanistically enriched patient enrolment, and incorporation of biological and tissue-level reperfusion endpoints alongside conventional functional outcomes. Ultimately, closing the reperfusion–outcome gap will require moving beyond empirical, universal drug administration toward a precision, pharmacologically augmented EVT paradigm that aligns adjunctive therapy with mechanism-specific procedural phenotypes and prioritizes true tissue-level recovery over angiographic success alone. Full article

(This article belongs to the Special Issue Acute Ischemic Stroke Management Strategies)

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23 pages, 761 KB

Open AccessReview

Deep Vein Thrombosis Prevention in Acute Ischemic Stroke Patients with Lower Limb Paralysis: A Narrative Review

by Jianyu Peng, Shiyan Long and Ling Feng

J. Clin. Med. 2026, 15(6), 2091; https://doi.org/10.3390/jcm15062091 - 10 Mar 2026

Cited by 2 | Viewed by 3572

Abstract

Patients with lower limb paralysis following acute ischemic stroke (AIS) are at a markedly increased risk of deep vein thrombosis (DVT), which may lead to pulmonary embolism and substantially higher mortality and disability. This review comprehensively reviews studies from the past decade on the epidemiology, pathophysiology, and prevention of DVT in AIS patients with lower limb paralysis. The pathogenesis of DVT in this population is multifactorial, involving venous stasis due to immobility, stroke-induced hypercoagulability, endothelial dysfunction, neutrophil extracellular trap-mediated immunothrombosis, and autonomic dysregulation. Effective prevention requires individualized risk stratification, integrating clinical assessment, biomarkers, and imaging tools. Current prophylactic strategies include pharmacological anticoagulation (primarily low-molecular-weight heparin), mechanical interventions (such as intermittent pneumatic compression), and early mobilization and rehabilitation. While combined approaches have demonstrated significant benefits, challenges remain regarding the timing of anticoagulation, balancing bleeding risks, extended thromboprophylaxis, and novel immunothrombosis targets. Future research should focus on personalized prevention protocols, the application of artificial intelligence-based predictive models, and innovative therapies targeting endothelial injury and immune-mediated thrombosis, aiming to improve thromboprophylaxis and overall outcomes in this high-risk population. Full article

(This article belongs to the Special Issue Acute Ischemic Stroke Management Strategies)

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35 pages, 3665 KB

Open AccessReview

Parent Artery Disease-Related Stroke: What Is the Impact on Endovascular Treatment? A Narrative Review

by Marialuisa Zedde, Francesca Romana Pezzella, Piergiorgio Lochner and Rosario Pascarella

J. Clin. Med. 2026, 15(3), 983; https://doi.org/10.3390/jcm15030983 - 26 Jan 2026

Viewed by 1444

Abstract

Background/Objectives: Parent artery disease (PAD) is a significant yet often overlooked contributor to ischemic strokes, particularly affecting the perforating arteries. This study aims to evaluate the impact of PAD on endovascular treatment outcomes in patients with intracranial atherosclerosis. Methods: A narrative review was conducted, synthesizing the existing literature on PAD and its relationship with endovascular interventions. Key studies were analyzed to assess the effectiveness of imaging techniques like high-resolution Magnetic Resonance Imaging (MRI) and the implications of plaque morphology on treatment strategies. Results: The findings indicate that PAD significantly complicates endovascular procedures, often leading to perforating artery occlusions and increased rates of stroke recurrence. Patients with PAD-related strokes demonstrated larger lesion volumes and more severe neurological deficits compared to those with small vessel disease. The review highlights the challenges of accurately diagnosing PAD using conventional imaging techniques, emphasizing the need for advanced modalities to identify atheromatous plaques that may not cause significant stenosis. Conclusions: The study underscores the necessity for a shift in clinical practice towards recognizing and managing PAD in patients with ischemic strokes. Enhanced imaging techniques and tailored endovascular strategies are essential to improve patient outcomes and minimize the risk of recurrent strokes. Further research is needed to establish comprehensive guidelines for addressing PAD in acute stroke management. Full article

(This article belongs to the Special Issue Acute Ischemic Stroke Management Strategies)

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