Abstract
Outcomes in acute ischemic stroke (AIS) depend critically on rapid and accurate early diagnosis in the emergency department. Traditional prehospital tools and large vessel occlusion–focused scales facilitate triage but have limited capacity to distinguish ischemic from hemorrhagic stroke, a distinction essential for acute-phase treatment decisions. Recent advances include mobile stroke units equipped with computed tomography (CT), point-of-care laboratories, and telemedicine systems, as well as the emergence of biomarkers that enable field-based diagnosis and faster initiation of therapy. In-hospital imaging strategies incorporating CT, CT perfusion, and magnetic resonance imaging (MRI)-based tissue clocks have expanded eligibility for endovascular thrombectomy to include patients with large-core infarction or unclear-onset wake-up strokes. Prolonged cardiac monitoring and high-resolution vessel wall MRI have improved the detection of embolic sources and high-risk atherosclerotic plaques. Artificial intelligence now supports rapid imaging interpretation, workflow optimization, and treatment selection. Tenecteplase, a novel thrombolytic, provides a practical alternative to alteplase with comparable safety and efficacy, while post-thrombectomy management emphasizes individualized blood pressure control. In patients with minor stroke or high-risk transient ischemic attack, short-term dual antiplatelet therapy reduces early recurrence, and early initiation of lipid-lowering agents after AIS may stabilize vulnerable plaques and enhance vascular outcomes. Collectively, these innovations represent a shift toward integrated, time-sensitive, and precision-based AIS care spanning prehospital assessment, emergency department management, and post-reperfusion management.
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Keywords: Acute ischemic stroke; Artificial intelligence; Prehospital care; Rapid diagnosis; Acute thrombolysis; Stroke management
Capsule Summary
What is already known
Outcomes in acute ischemic stroke are highly time-dependent, with rapid and accurate diagnosis being essential for effective treatment. Conventional prehospital triage tools aid in identifying stroke symptoms and assessing severity but have limited ability to distinguish ischemic from hemorrhagic stroke or to guide treatment decisions beyond standard time windows. Intravenous alteplase has long been the standard thrombolytic therapy, while endovascular thrombectomy is firmly established for large vessel occlusion within conventional eligibility criteria. In addition, secondary prevention through antiplatelet therapy and lipid-lowering strategies has traditionally been emphasized from the acute phase through the chronic phase.
What is new in the current study
Recent advances are transforming acute stroke care toward a more integrated, data-driven, and precision-based model. Mobile stroke units, point-of-care biomarkers, and telemedicine now enable field-based diagnostic confirmation and earlier initiation of therapy. Imaging innovations, including computed tomography– and magnetic resonance imaging (MRI)-based tissue clocks, have expanded eligibility for endovascular thrombectomy to patients with large infarct cores and strokes of unclear onset. High-resolution vessel wall MRI and prolonged cardiac monitoring facilitate improved detection of high-risk atherosclerotic plaques and covert cardioembolic sources. Artificial intelligence increasingly supports acute stroke care by accelerating imaging interpretation, streamlining workflow, and monitoring posttreatment complications. Moreover, tenecteplase has emerged as a practical alternative to alteplase, offering comparable safety and efficacy with simplified single-bolus administration. Early initiation of dual antiplatelet therapy and lipid-lowering agents, including proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, further suggests new opportunities to reduce recurrence and stabilize vulnerable plaques even during the acute phase of stroke management.
INTRODUCTION
Few conditions in emergency medicine rival acute ischemic stroke (AIS) in the urgency of diagnosis and treatment. In emergent large vessel occlusion (LVO), each minute without reperfusion results in irreversible neuronal loss and worsened long-term outcomes [
1]. For emergency physicians, the first hours represent not only a race against time but also a critical window of opportunity in which rapid, well-informed decisions can dramatically alter a patient’s outcome—from severe disability to functional independence.
Historically, prehospital and emergency department (ED) stroke assessment has relied on clinical scales for triage, but these tools are limited in distinguishing ischemic from hemorrhagic stroke and in identifying the underlying stroke etiology [
2]. Recent innovations, such as mobile stroke units with onboard imaging, point-of-care testing, advanced imaging protocols, and biomarker-based assays, now enable faster and more accurate stroke classification [
3]. Prolonged cardiac monitoring and high-resolution vascular imaging further improve detection of cardioembolic sources and high-risk atherosclerotic plaques, helping identify the cause of ischemic stroke [
4]. Artificial intelligence (AI) has extended its role beyond image interpretation to real-time clinical decision support, guiding eligibility for reperfusion therapies including intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT).
Therapeutic advances are reshaping AIS care in the ED. New thrombolytic agents offer simplified administration with comparable or improved outcomes relative to current standards [
5]. EVT indications have broadened to include large core, distal vessel, and posterior circulation strokes, guided by advanced imaging criteria and extended treatment windows [
6]. Early implementation of adjunctive pharmacologic interventions, such as short-term dual antiplatelet therapy and early lipid-lowering therapy, may further decrease recurrence risk and enhance long-term vascular outcomes [
7]. This review synthesizes recent developments in diagnosis and treatment, providing emergency physicians with practical, evidence-based insights to optimize stroke care from arrival to reperfusion.
PREHOSPITAL DIAGNOSIS: FROM TRIAGE TO ON-SITE DETECTION
Early identification of AIS in the prehospital setting has traditionally relied on clinical scoring systems such as the Cincinnati Prehospital Stroke Scale (CPSS) or the Los Angeles Prehospital Stroke Screen (LAPSS), as well as LVO-focused tools like the Rapid Arterial Occlusion Evaluation (RACE) [
8–
10]. These scales aid in recognizing stroke symptoms and estimating severity, facilitating transport to EVT-capable centers. However, their ability to distinguish ischemic from hemorrhagic stroke, the most critical determinant for initiating appropriate acute-phase reperfusion therapy, remains limited, and variability in provider training, patient presentation, and scale selection affects reliability [
11].
Prehospital stroke care is increasingly shifting toward direct field diagnostics (
Table 1) [
3,
8–
21]. Mobile stroke units (MSUs), equipped with onboard computed tomography (CT) scanners, point-of-care laboratories, and telemedicine connectivity, enable imaging and treatment initiation before hospital arrival [
3. Randomized and observational studies have shown that MSUs reduce onset-to-needle times by 20 to 40 minutes and increase the proportion of patients treated within the “golden hour.” Concurrently, blood-based biomarkers such as glial fibrillary acidic protein (GFAP) show promise for differentiating intracerebral hemorrhage from AIS both in prehospital environments (e.g., ambulances or MSUs) and in the ED. Point-of-care GFAP assays can provide results within minutes, refining thrombolysis eligibility and guiding transport strategies [
12]. Together, these innovations may transition prehospital AIS care from symptom-based triage to rapid, on-site diagnostic confirmation. Advances in field-based diagnostics enable critical treatment decisions to be made immediately upon ED arrival. However, without imaging confirmation, precise treatment eligibility remains uncertain, underscoring the importance of next-generation stroke imaging strategies to expand EVT opportunities.
INITIAL IMAGING TO EXPAND EVT ELIGIBILITY
Recent advances in AIS imaging have focused on identifying large-core infarcts using CT and applying tissue clock concepts to select patients for EVT beyond conventional time windows [
13,
14]. The RESCUE-Japan LIMIT, ANGEL-ASPECT, and SELECT2 trials demonstrated that patients with an Alberta Stroke Program Early CT Score (ASPECTS) of 3–5 or a CT perfusion (CTP) core volume of ≥50–70 mL can still benefit from EVT, marking a shift away from excluding large-core patients [
13,
15,
16]. Simple CT metrics such as ASPECTS and CTP-derived core estimates are now central to patient selection, while AI-driven alert systems in hub-and-spoke networks have been shown to shorten door-to-puncture times. Because CTP may overestimate core size within the first 3 hours, integrating ASPECTS, clinical presentation, and collateral status from single-phase or multiphase CT angiography (CTA) remains important.
For strokes with unclear onset, particularly wake-up strokes, imaging surrogates such as the diffusion-weighted imaging–fluid-attenuated inversion recovery mismatch can approximate onset time. The WAKE-UP trial and subsequent pooled analyses showed that this mismatch corresponds to a lesion age of about 3 hours, with more than 80% of cases occurring within 4.5 hours, thereby enabling safe IVT in patients previously considered ineligible. In the WAKE-UP trial, a modified Rankin scale (mRS) score of 0–1 at 90 days was achieved in 53.3% of patients compared with 41.8% in the placebo group [
17]. Thus, imaging technologies are extending eligibility for both IVT and EVT beyond traditional temporal limits. Refinement of patient selection also enhances the identification of stroke etiology, particularly in cases of undetermined origin, which is crucial for guiding optimal secondary prevention strategies.
FINDING THE CULPRIT FOR STROKE
In patients with embolic stroke of undetermined source (ESUS), large randomized trials such as NAVIGATE ESUS and RE-SPECT ESUS failed to demonstrate the superiority of direct oral anticoagulants over aspirin for secondary prevention [
22,
23]. These findings have redirected attention toward identifying covert cardioembolic sources, particularly paroxysmal atrial fibrillation (AF). Prolonged cardiac monitoring significantly increases AF detection: the EMBRACE trial showed that 30-day external event monitoring detected AF in 16.1% of patients compared with 3.2% using 24-hour Holter monitoring, while the CRYSTAL-AF study found that implantable loop recorders identified AF in 12.4% of patients at 12 months, rising to 30% at 3 years [
24,
25]. Patch-type continuous electrocardiogram monitors now provide a less invasive, patient-friendly alternative to implantable loop recorders, maintaining high diagnostic yield over several weeks. Ongoing prospective trials, such as the Korean SOLO-ESUS study, are evaluating the clinical utility and cost-effectiveness of these devices in guiding secondary prevention in ESUS [
26].
High-resolution vessel wall magnetic resonance imaging (VW-MRI) is increasingly vital for characterizing intracranial atherosclerosis (ICAS) and identifying high-risk plaques associated with recurrent ischemic events. Beyond assessing luminal stenosis, VW-MRI can reveal intraplaque hemorrhage, lipid-rich necrotic core, irregular surfaces, and strong post-contrast enhancement [
27]. In ICAS, culprit plaques with enhancement are correlated with higher recurrence rates and artery-to-artery embolism, suggesting that plaque inflammation and instability contribute to embolic events even in the absence of severe stenosis. The 4D flow-MRI studies have demonstrated that high wall shear stress is associated with plaque enhancement [
28]. Vascular tortuosity has also been linked to ICAS development and altered local hemodynamics, potentially increasing plaque vulnerability. These findings underscore the importance of integrating structural and hemodynamic evaluations—via VW-MRI and flow modeling—for improved risk stratification and targeted prevention in ICAS and other intracranial vasculopathies.
USE OF AI IN THE ACUTE STAGE OF STROKE
AI has evolved from a tool for image postprocessing to a comprehensive decision-support system in AIS. The Rapid platform (iSchemaView Inc), one of the first widely adopted solutions, provides automated CT perfusion and MRI diffusion/perfusion analyses to rapidly quantify infarct core and penumbra. Its application in late-window thrombectomy trials such as DAWN and DEFUSE 3 demonstrated how automated imaging can standardize patient selection and accelerate treatment decisions across institutions [
18,
19]. More recently, AI has been applied to strokes of unclear onset, with models trained on imaging and clinical features predicting onset within 6 hours with greater than 80% accuracy, complementing tissue clock–based selection methods [
29].
In Korea, AI platforms now perform fully automated LVO detection on CTA, ASPECTS scoring on noncontrast CT, and core-penumbra estimation on CT perfusion, all with processing times of only a few minutes [
20]. Multicenter studies have shown high concordance with expert neuroradiologists (intraclass correlation coefficients of 0.6–0.8 for ASPECTS, and sensitivity for LVO exceeding 90%), as well as measurable workflow improvements in door-to-puncture times when AI triage alerts are used [
21]. Some systems also extend to posttreatment monitoring, detecting hemorrhagic transformation or malignant edema on follow-up imaging. These developments illustrate a transition toward AI as a platform not only for patient selection but also for therapy prioritization, complication monitoring, and quality improvement. With expanding regulatory approvals and integration into clinical workflows, AI-based decision support is poised to become a standard component of acute stroke care in Korea and globally. Acute treatment strategies and early secondary prevention approaches for AIS are summarized in
Table 2 [
5,
13,
15–
19,
30–
43].
Tenecteplase, a genetically modified variant of alteplase with higher fibrin specificity and a longer half-life, enables single-bolus administration, thereby simplifying workflow and potentially reducing door-to-needle time [
30–
34] (
Table 2). Multiple randomized controlled trials have compared tenecteplase with standard-dose alteplase. In the EXTEND-IA TNK trial, patients eligible for EVT who received tenecteplase 0.25 mg/kg achieved higher pre-procedure reperfusion rates (22% vs. 10%, P=0.002) and better 90-day functional outcomes, without an increase in symptomatic intracranial hemorrhage [
30]. The ATTEST trial demonstrated similar early neurological improvement and safety [
31], with a trend toward greater reperfusion in the tenecteplase group [
32].
Large-scale studies have reinforced these findings in broader AIS populations. The AcT trial, involving 1,577 patients within 4.5 hours of onset, showed that tenecteplase 0.25 mg/kg was noninferior to alteplase in achieving an mRS score of 0–1 at 90 days (36.9% vs. 34.8%; risk difference, 2.1%; 95% confidence interval [CI], –2.6 to 6.9) with no difference in symptomatic hemorrhage [
33]. The TRACE-2 trial in China confirmed noninferiority in an Asian cohort [
34]. Meta-analyses indicate that tenecteplase offers at least equivalent functional outcomes, with potential advantages in reperfusion and operational efficiency [
44,
45].
Given its ease of administration, favorable workflow impact, and comparable safety profile, international guidelines increasingly recognize tenecteplase, particularly at a dose of 0.25 mg/kg, as a practical alternative to alteplase in eligible AIS patients. Ongoing studies are investigating its use in extended time windows, wake-up strokes, and other subgroups, potentially further expanding its role in acute reperfusion therapy.
EVT in AIS
EVT for large ischemic cores is now supported by multiple randomized controlled trials [
13,
15,
16] (
Table 2). In RESCUE-Japan LIMIT (ASPECTS 3–5 or MRI-guided ≤24 hours), an mRS of 0–3 at 90 days was achieved in 31.0% of EVT patients compared with 12.7% receiving medical therapy (risk ratio [RR], 2.43), although any intracranial hemorrhage occurred more frequently in the EVT group (58.0% vs. 31.4%) [
15]. ANGEL-ASPECT (ASPECTS 3–5 or core 70–100 mL; ≤24 hours) demonstrated a favorable shift in mRS distribution (generalized odds ratio [OR], 1.37; 95% CI, 1.11–1.69), with symptomatic intracranial hemorrhage in 6.1% vs. 2.7% [
16]. SELECT2 (ASPECTS 3–5 or core ≥50 mL; ≤24 hours) was terminated early for efficacy, showing an mRS shift OR of 1.51 (95% CI, 1.20–1.89) and functional independence in 20% vs. 7% (RR, 2.97), with no increase in mortality [
13].
For unclear-onset and late-window strokes, imaging-based selection remains central. In DAWN (last known well 6–24 hours; clinical-core mismatch), functional independence was achieved in 49% vs. 13%, with an mRS shift of 5.5 vs. 3.4. DEFUSE 3 (6–16 hours; CTP mismatch) showed an mRS 0–2 in 45% vs. 17%, and mortality was lower (14% vs. 26%). Nevertheless, pooled late-window data reveal substantial residual disability: in DEFUSE 3, 39% had an mRS ≥4, and in DAWN, 42%, underscoring the need for careful preprocedural counseling. EVT for posterior circulation occlusion has also expanded: the ATTENTION trial (basilar artery ≤24 hours) achieved mRS 0–3 in 46% vs. 23% with medical management, supporting EVT beyond conventional limits in selected patients [
18,
19,
35].
Blood pressure (BP) control after EVT is crucial to prevent reperfusion injury, hemorrhagic transformation, and infarct expansion. Higher postprocedural systolic BP and greater BP variability have been linked to poorer outcomes and higher symptomatic intracranial hemorrhage risk. The OPTIMAL-BP trial randomized patients after successful endovascular thrombectomy to intensive systolic BP lowering (<140 mmHg) versus a standard target (140–180 mmHg) within 1 hour of recanalization. At 90 days, functional independence (mRS ≤2) was lower in the intensive group (39.4%) than in the standard group (54.4%), suggesting no benefit—and possible harm—from aggressive BP reduction [
36] (
Table 2).
ANTIPLATELET AND LIPID MANAGEMENT IN THE ACUTE STAGE
Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel is supported for acute minor ischemic stroke and high-risk transient ischemic attack. In CHANCE trial (n=5,170), 21-day DAPT reduced 90-day recurrent stroke (8.2% vs. 11.7%; hazard ratio [HR], 0.68) without an increase in major bleeding; subgroup analyses showed greater benefit in patients with large-artery atherosclerosis and those treated within 12 hours of onset [
37]. The POINT trial (n=4,881) confirmed efficacy (5.0% vs. 6.5%; HR, 0.75) but showed higher rates of major hemorrhage (0.9% vs. 0.4%); benefits were concentrated in the first 21 days [
38]. The INSPIRES trial (n=6,100), enrolling patients with ≥50% stenosis, showed reduced new stroke (7.3% vs. 9.2%; HR, 0.79) but higher moderate-to-severe bleeding (0.9% vs. 0.4%); effects were consistent across intracranial and extracranial disease [
39]. The THALES trial (n=11,016) found that aspirin-ticagrelor reduced 30-day stroke or death (5.5% vs. 6.6%; HR, 0.83), with the greatest benefit in ipsilateral large-artery atherosclerosis but a higher rate of severe bleeding (0.5% vs. 0.1%) [
40] (
Table 2).
Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, including evolocumab and alirocumab, have demonstrated in coronary artery disease that early initiation can rapidly lower low-density lipoprotein cholesterol and promote plaque stabilization, as evidenced by intravascular imaging studies such as GLAGOV and PACMAN-AMI [
41,
42] (
Table 2). In ischemic stroke, particularly in Chinese cohorts, small prospective studies have investigated early post-AIS use, reporting significant low-density lipoprotein cholesterol reduction, improved plaque characteristics on vessel wall MRI [
43], and favorable modulation of inflammatory markers within weeks. While these findings suggest a potential role in secondary prevention beginning in the acute phase, no large randomized trials have yet confirmed benefits on short-term neurological outcomes. Further studies are needed to determine whether early PCSK9 inhibitor therapy after AIS can reproduce the plaque-stabilizing and event-reducing effects observed in acute coronary syndrome.
CONCLUSION
The landscape of AIS care is rapidly evolving, with advances in prehospital diagnostics, imaging technologies, reperfusion therapies, and pharmacologic strategies expanding treatment opportunities and improving clinical outcomes. The integration of MSUs, point-of-care biomarkers, and AI-driven decision-support systems represents a shift toward rapid, mechanism-informed intervention. Moving forward, the successful translation of these innovations into routine clinical practice will depend not only on robust supporting evidence but also on seamless, multidisciplinary collaboration among emergency medicine, neurology, radiology, neurosurgery, and rehabilitation teams to ensure timely, coordinated, and comprehensive stroke care.
NOTES
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Author contributions
Conceptualization: SHH, SK, BJK; Investigation: SHH, SK, BJK; Methodology: SMK, JP, SEL, BJK; Resources: SMK, JP, SEL, BJK; Supervision: SMK, JP, SEL, BJK; Visualization: SMK, JP, SEL, BJK; Writing–original draft: SHH, SK, BJK; Writing–review & editing: all authors. All authors read and approved the final manuscript.
-
Conflicts of interest
The authors have no conflicts of interest to declare.
-
Funding
The authors received no financial support for this study.
-
Data availability
Data sharing is not applicable as no new data were created or analyzed in this study.
Table 1.Rapid diagnosis and triage in the ED
Table 1.
|
Tool |
Implication for ED practice |
Key evidence |
Consideration |
|
Mobile stroke unit |
CT/POC/telemedicine before arrival → Faster IVT/EVT |
Onset-to-needle ↓ 20–40 min [3] |
Limited availability |
|
↑ Golden-hour treatment [3] |
|
GFAP POC test |
Rapid ICH vs. AIS differentiation in prehospital and ED |
Results in minutes [11,12] |
Still needs imaging confirmation |
|
Improves triage accuracy [11,12] |
|
Clinical scale (CPSS, LAPSS, RACE) |
Quick triage |
Simple, widely used [8–10] |
Cannot distinguish ICH vs. AIS |
|
Identify LVO for EVT referral |
|
Initial CT/CTA/CTP (±AI support) |
Identify large core, LVO, collaterals |
Large-core patients benefit from EVT [13–16] |
CTP may overestimate core <3 hr |
|
AI shortens door-to-puncture time [18–21] |
|
DWI-FLAIR mismatch (tissue clock) |
Expands IVT to wake-up/unclear-onset stroke |
WAKE-UP trial: mRS 0–1 at 90 days, 53.3% vs. 41.8% [17] |
Requires MRI |
Table 2.Acute treatment and early secondary prevention
Table 2.
|
Therapy |
Implication for ED practice |
Benefit |
Risk/consideration |
|
Alteplase (tPA) |
0.9 mg/kg infusion ≤4.5 hr |
Standard treatment [5,17] |
Infusion time, monitoring |
|
Tenecteplase |
0.25 mg/kg single bolus ≤4.5 hr |
Higher fibrin specificity; longer half-life noninferior to tPA [30–34] |
Not yet approved for AIS in Korea (regulatory review ongoing) |
|
EVT reperfusion 22% vs. 10% [30] |
|
EVT |
|
|
|
|
Large core |
ASPECTS 3–5, core ≥50–70 mL |
Functional independence ↑ [13,15,16] |
Higher ICH risk |
|
Late/unknown onset |
DAWN trial [18]: 6–24 hr |
mRS 0–2: |
Substantial residual disability |
|
DEFUSE 3 trial [19]: 6–16 hr |
49% vs. 13% [18] |
|
45% vs. 17% [19] |
|
Posterior circulation occlusion |
ATTENTION trial [35]: basilar artery ≤24 hr |
mRS 0–3: 46% vs. 23% with medical care [35] |
Prompt transfer essential due to rapid deterioration |
|
Post-EVT BP target |
Keep SBP 140–180 mmHg (avoid <140 mmHg early) |
OPTIMAL-BP trial [36]: better outcomes with standard vs. intensive |
No benefit and potential harm from intensive lowering |
|
Short-term DAPT |
|
|
|
|
Aspirin+Clopidogrel |
Minor stroke/TIA |
Reduced recurrent stroke |
Bleeding ↑ if >21–30 days |
|
CHANCE trial [37]: 8.2% vs. 11.7% |
|
POINT trial [38]: 5.0% vs. 6.5% |
|
INSPIRES trial [39]: 7.3% vs. 9.2% |
|
Aspirin+Ticagrelor |
Alternative DAPT option, faster onset, CYP2C19-independent |
Lowered 30-day stroke/death |
Severe bleeding ↑ (0.5% vs. 0.1%) |
|
THALES trial [40]: 5.5% vs. 6.6% |
|
High-intensity statin (±PCSK9 inhibitor) |
Initiate in ED |
Rapid LDL-C ↓; plaque stabilization [41–43] |
No large RCT on short-term neurological outcomes |
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