A Clinical Study on the Improvement of Cognitive Function in Symptomatic Non-Acute Internal Carotid Artery Occlusion Patients with Hasan Type A and B

Summary

This study aimed to compare vascular reperfusion with conservative treatment in patients with Hasan type A/B symptomatic NA-ICAO.

Abstract

Symptomatic non-acute internal carotid artery occlusion (NA-ICAO), particularly Hasan type A/B, is characterized by persistent cerebral hypoperfusion that may lead to neurological and cognitive impairment. Endovascular recanalization therapy (EVT) aims to restore cerebral blood flow and improve functional outcomes in patients with these conditions. A total of 66 patients with symptomatic NA-ICAO admitted between June 2022 and October 2023 were randomly assigned to an EVT group (n = 32) or a conservative medical therapy group (n = 34). Neurological and cognitive functions were evaluated before treatment and at 3 and 12 months after treatment using standardized scales, including the modified Rankin Scale (mRS), National Institutes of Health Stroke Scale (NIHSS), Mini-Mental State Examination (MMSE), and Montreal Cognitive Assessment (MoCA). Recanalization was successfully achieved in all 32 patients, with 9 cases reaching TICI grade 2b and 23 cases reaching TICI grade 3. Among 32 patients undergoing EVT, 12 (37.5%) experienced perioperative adverse events, including 2 (6.25%) serious events. At 3 months, the mRS score was significantly lower in the EVT group than in controls. At 12 months, the EVT group showed significantly greater improvements in MMSE, mRS, and MoCA scores, with the largest effect size observed for MoCA (Cohen's d = 0.82). Domain-specific analysis revealed significant improvement in language ability. EVT may offer potential clinical benefits for selected patients with chronic carotid occlusion; however, larger multicenter studies are warranted to confirm its long-term efficacy and safety.

Introduction

Ischemic stroke remains one of the leading causes of mortality and long-term disability worldwide, and internal carotid artery occlusion (ICAO) is a major etiological factor contributing to its occurrence¹. When the occlusion of the internal carotid artery persists for more than 24 h, it is defined as non-acute internal carotid artery occlusion (NA-ICAO)². The clinical manifestations of NA-ICAO largely depend on the compensatory capacity of the intracranial collateral circulation³. Patients with sufficient collaterals are often asymptomatic or present only mild symptoms, with a relatively low risk of stroke⁴. in contrast, those with poor collateral compensation commonly exhibit limb weakness, cognitive impairment, transient ischemic attacks (TIA), or stroke⁵. In addition, some NA-ICAO patients may show perfusion deficits or ischemic changes on neuroimaging⁶. Determining the optimal therapeutic strategy for symptomatic NA-ICAO remains a major clinical challenge.

Currently, therapeutic strategies for symptomatic NA-ICAO include medical management, extracranial-intracranial bypass, carotid endarterectomy (CEA), and endovascular therapy^7,8,9,10. Medical therapy remains the most commonly used initial approach, particularly for patients with mild symptoms or adequate collateral compensation¹¹. Since Terada et al. first reported successful recanalization of NA-ICAO using EVT in 2005¹², this technique has gradually become an important treatment option. Accumulating evidence suggests that EVT can effectively improve cerebral hemodynamics and perfusion, reduce stroke recurrence, and enhance long-term neurocognitive outcomes¹³. However, variations in vascular morphology and collateral circulation significantly influence the success rate and clinical outcomes of EVT. Hasan et al.¹⁴ classified ICAO into four types (A-D) based on the morphology of the occluded stump and the presence of distal collateral reflux. Type A is characterized by a patent proximal stump, short occlusion segment, and good distal filling, whereas Type B presents a tapered stump with retrograde flow through the ophthalmic or anterior communicating arteries. Previous studies have shown that patients with Hasan A/B morphology and usable collaterals are more likely to benefit from EVT^15,16. Although EVT offers potential advantages in improving outcomes for NA-ICAO patients, it still carries limitations such as recanalization failure and perioperative complications, particularly in patients with complex vascular anatomy or insufficient collaterals¹⁷. Based on the Hasan classification, this study focused on symptomatic NA-ICAO patients with A/B morphology, comparing the efficacy and safety of EVT versus conservative medical therapy. The detailed inclusion criteria and imaging evaluation methods are described in the PROTOCOL section. This study aims to evaluate the potential of EVT in improving neurological and cognitive function, thereby providing evidence to guide individualized treatment decisions for this specific patient population.

Protocol

Eligible patients were recruited at the Department of Neurological Critical Care, Weifang Traditional Chinese Medicine Hospital. All potential participants were consecutively screened using predefined inclusion and exclusion criteria by two independent neurologists. Baseline demographic and clinical information was collected from the hospital electronic medical record system using a standardized data extraction form. Formal approval for the study protocol was obtained from the Medical Research Ethics Committee of Weifang Traditional Chinese Medicine Hospital (Approval No. 2024YX091) prior to initiation of the study. All study procedures were conducted in accordance with the principles of the Declaration of Helsinki. Written informed consent was obtained from all participants or their legally authorized representatives before enrollment. Figure 1 illustrates a flow diagram of participant enrollment, allocation, follow-up, and analysis. The consumables and the equipment used are listed in the Table of Materials.

1. Patient assessment

1. Inclusion criteria
Internal carotid artery occlusion (ICAO) was confirmed using digital subtraction angiography (DSA), which was independently reviewed by two experienced interventional neuroradiologists. The occlusion was classified as Hasan type A or B according to the Hasan classification system. An occlusion duration of ≥24 h was verified. Clinical symptoms attributable to the occluded artery, including ischemic stroke, transient ischemic attack, transient monocular blindness (amaurosis fugax), or syncope, were confirmed based on neurological examination and imaging correlation. Cerebral perfusion status was assessed using magnetic resonance perfusion (MRP) or computed tomography perfusion (CTP) imaging. Hypoperfusion in the hemisphere ipsilateral to the occluded artery was identified as an eligibility requirement. All diagnostic and confirmatory procedures were performed using standardized imaging acquisition and clinical assessment protocols to ensure diagnostic accuracy and reproducibility.

2. Exclusion criteria
Patients with a documented allergy or contraindication to antithrombotic agents, anesthetic drugs, or iodinated contrast media used during DSA were excluded based on preoperative allergy history review and relevant laboratory testing. Patients with evidence of prior infarction involving key cognitive regions (including the hippocampus, thalamus, or angular gyrus), severe leukoencephalopathy, or coexisting neurological disorders known to impair cognition, such as Alzheimer's disease, were excluded based on neuroimaging and clinical evaluation. Patients who were unable to complete neurological or cognitive assessments due to global aphasia or major psychiatric disorders (including depression, anxiety, or psychosis) were excluded following neurological and psychiatric consultation. Patients with severe systemic comorbid disease and an estimated life expectancy of less than 1 year were excluded, as judged by the treating physician based on comprehensive clinical and laboratory data. After completion of patient screening and enrollment, standardized preoperative pharmacological preparation was initiated to minimize thromboembolic and ischemic risks prior to intervention.

2. Preoperative antiplatelet and lipid-lowering therapy

Dual antiplatelet therapy was initiated 3-5 days before EVT, consisting of enteric-coated aspirin (100 mg/day) and clopidogrel (75 mg/day) to reduce perioperative thromboembolic risk. Atorvastatin (20 mg/day) was administered concurrently to lower lipid levels and stabilize atherosclerotic plaques. The antithrombotic regimen was adjusted based on individualized risk assessment in patients with a high bleeding risk or drug intolerance.

3. Imaging and vascular assessment

Preoperative vascular imaging was performed to determine the occlusion site, occlusion segment length, distal vessel patency, and collateral circulation status. Magnetic resonance angiography (MRA) or computed tomography angiography (CTA) was used for the initial vascular evaluation. Typical preoperative MRA features were identified, including complete absence of flow in the affected internal carotid artery (ICA) and markedly reduced visualization of the ipsilateral middle cerebral artery (MCA) branches, as illustrated in Figure 2A.

All MR examinations were performed using a 3.0-Tesla MR scanner. CT and angiographic scans were acquired using a 128-slice CT system. Both imaging systems were maintained and calibrated in accordance with manufacturer specifications and institutional quality-control standards to ensure image consistency. Iodixanol (320 mg I/mL, 80-100 mL) was used as the contrast agent during angiography.

Perfusion imaging, including CT perfusion (CTP) or MR perfusion (MRP), was performed to assess the ischemic penumbra and tissue viability (Figure 2B- D). Quantitative perfusion maps, including cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT), were generated and analyzed. Two independent neuroradiologists were assigned to perform all perfusion image analyses. Ipsilateral hemispheric hypoperfusion was confirmed when CBF was reduced by >30% compared with the contralateral side, with preserved CBV.

During diagnostic DSA, expected visualization cues were carefully verified to confirm true-lumen entry and collateral adequacy. True-lumen entry was defined when the contrast agent filled the distal internal carotid artery smoothly without reflux or subintimal staining. Collateral circulation via the external carotid artery (ECA) and anterior communicating artery (ACoA) was assessed by observing retrograde opacification of the intracranial ICA or MCA branches during delayed arterial and venous phases. All imaging findings were jointly interpreted by two experienced neuroradiologists, and any discrepancies were resolved by consensus to ensure reproducibility and accuracy of vascular assessment.

4. Optimization of the general condition

Blood pressure, blood glucose, and electrolyte levels were optimized before the intervention to ensure procedural safety. The surgical objectives, potential risks, and possible complications were explained in detail to the patient and family members. Written informed consent was obtained from the patient or their legally authorized representatives. After physiological stability and surgical readiness were confirmed, the patient was transferred to the angiography suite for the endovascular procedure under general anesthesia.

1. Anesthesia and positioning
All procedures were performed under general anesthesia in a hybrid DSA operating room maintained at a temperature of 24 °C and a relative humidity of 50%-60% (following institutionally approved protocols). The patient's core body temperature was continuously monitored and maintained between 36 °C and 37 °C using a circulating warming blanket. The patient was positioned supine with the head slightly extended and rotated contralaterally to optimize catheter navigation and fluoroscopic visualization of the carotid artery and intracranial circulation.

2. Arterial access and guiding catheter placement
Routine sterile skin preparation and draping were performed. The right femoral artery was punctured, and an 8F arterial sheath was introduced. An 8 F guiding catheter was advanced under fluoroscopic guidance to the distal segment of the common carotid artery on the affected side. Initial DSA was performed to confirm complete occlusion of the target ICA with a residual stump at its origin, as shown in Figure 2E.

3. Crossing the occluded segment
A microguidewire was carefully advanced across the occluded segment of the ICA under continuous roadmap guidance. Once the guidewire had traversed the lesion, a microcatheter was advanced along the established track to the level of the ophthalmic artery. After withdrawal of the guidewire, a small amount of contrast was gently injected through the microcatheter to verify intraluminal positioning. True-lumen entry was confirmed when contrast opacified the distal ICA in a smooth, antegrade fashion without evidence of reflux, delayed clearance, or subintimal staining. When contrast pooling, irregular filling patterns, or reflux were observed, the guidewire was repositioned, and passage was reattempted to avoid subintimal advancement or vessel injury. Collateral circulation was assessed by confirming retrograde filling of the intracranial ICA via the ophthalmic artery supplied by the left ECA, as illustrated in Figure 2F. In addition, the absence of cross-flow from the right ICA through the ACoA was confirmed ( Figure 2G), as this finding may influence procedural strategy and perfusion dynamics.

5. Placement of the cerebral protection device

After true-lumen access was confirmed, a distal cerebral protection device was advanced along the microcatheter guidewire to the carotid siphon segment. The device was deployed to capture embolic debris generated during subsequent endovascular manipulation.

6. Balloon angioplasty and stent deployment

Following balloon dilation, angiography was performed to evaluate vessel patency. A self-expanding or balloon-expandable stent was implanted to cover the entire occluded segment when residual stenosis exceeded 40% or when significant elastic recoil was observed. Successful stent deployment was defined as complete stent apposition, continuous anterograde distal flow, and absence of contrast stagnation or edge dissection on angiography. The treated vessel was observed for approximately 20 min under real-time fluoroscopy to assess for delayed recoil.

All procedures were performed under continuous fluoroscopic guidance using iodixanol (320 mg I/mL, 80-100 mL) maintained at 24 °C to minimize viscosity-related variation in contrast flow. Distal cerebral protection devices (diameter 5.0-6.0 mm; including both domestic and imported models) were used as required during the procedure. Pre-dilation was performed with an intracranial balloon catheter (2.00 mm × 15 mm), followed by a drug-coated coronary balloon (4.0 mm × 30 mm). An appropriate stent was selected and implanted according to lesion morphology, including self-expanding tapered carotid stents (8-6 × 40 mm), self-expanding intracranial stents (4.0 mm × 20 mm), or balloon-expandable intracranial artery stents (3.0 mm × 13 mm), ensuring complete coverage of the diseased segment. After stent implantation, post-deployment angiography was performed to confirm satisfactory vessel patency, typically with residual stenosis of 30%-40%.

7. Reperfusion assessment and postoperative management

Post-deployment angiography was performed (Figure 2I), and recanalization was evaluated using the Thrombolysis in Cerebral Infarction (TICI) scale, with successful reperfusion defined as TICI grade 2b-3. Postoperative systolic blood pressure was maintained below 140 mmHg to reduce the risk of hyperperfusion injury or intracranial hemorrhage. Adequate intravenous hydration was provided to facilitate contrast-agent clearance. Dual antiplatelet therapy with aspirin (100 mg/day) and clopidogrel (75 mg/day), combined with lipid-lowering therapy, was continued for 3 months, followed by transition to single antiplatelet therapy thereafter. Follow-up CTA or DSA was performed within 24-48 h to confirm vessel patency. The patient was monitored for at least 72 h in the neurological intensive care unit (NICU) to detect potential complications. National consensus guidelines were followed for long-term pharmacologic management.

8. Neurological and cognitive function assessment

Neurological function was assessed using the National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Scale (mRS). Cognitive function was evaluated using the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). All assessments were performed at three time points: before treatment, 3 months after treatment, and 12 months after treatment.

9. Conservative medical therapy (control group)

Standardized conservative medical therapy was provided according to the 2019 Chinese Expert Consensus on the Revascularization Treatment of Chronic Internal Carotid Artery Occlusion. Dual antiplatelet therapy consisting of enteric-coated aspirin (100 mg/day) and clopidogrel (75 mg/day) was administered for 3 months, followed by single antiplatelet maintenance therapy. Atorvastatin calcium (20 mg/day) was administered to stabilize atherosclerotic plaques and control lipid levels. Strict vascular risk-factor management was implemented by maintaining blood pressure below 140/90 mmHg, or below 130/80 mmHg in patients with diabetes, and by optimizing glycemic control to maintain fasting glucose between 5.0-8.3 mmol/L, bedtime glucose between 5.6-10.0 mmol/L, and HbA1c below 8.0%. Individualized lifestyle counseling, including smoking cessation, salt restriction, and regular physical activity, was provided. Standardized rehabilitation therapy was offered under the supervision of a multidisciplinary team for patients with residual neurological deficits to promote functional recovery and cognitive improvement.

10. Data collection

General patient information, including age, sex, educational level, medical history, smoking status, and alcohol use, was collected. All neurological and cognitive assessment scores obtained from standardized evaluation tools were recorded. For symptomatic NA-ICAO patients, the revascularization success rate, post-procedural blood flow status, perioperative complications, restenosis rate of the treated vessel, and stroke recurrence rate were documented as procedural and follow-up outcomes.

11. Statistical analysis

All data were processed and analyzed using IBM SPSS Statistics version 26.0. A two-way repeated-measures ANOVA was performed to evaluate the longitudinal effects of Time, Treatment Group, and their interaction on neurological and cognitive function scores (mRS, NIHSS, MMSE, MoCA). The within-subject factor was defined as Time (T0, T1, T2), and the between-subject factor was defined as Treatment Group (vascular reperfusion therapy vs. conservative therapy). The analysis was accessed via Analyze → General Linear Model → Repeated Measures.

Mauchly's test of sphericity was used to examine the equality of the variance-covariance matrix. The Greenhouse-Geisser correction was applied when the sphericity assumption was violated (Options → Display → Estimates of effect size, Descriptive statistics, Homogeneity tests). When significant main effects or Time × Group interactions were detected, post-hoc multiple comparisons with Bonferroni correction were conducted to control type I error (Analyze → General Linear Model → Repeated Measures → Options → Compare main effects). For significant interactions, a simple effects analysis was performed to examine differences between time points within each treatment group as well as differences between treatment groups at each individual time point.

The simple effects analysis was accessed via Analyze → General Linear Model → Repeated Measures → Define → EM Means → Time by Group → Compare simple effects. Effect sizes were reported as partial η². Graphical representations (line plots with error bars) were generated to visualize longitudinal changes using Graphs → Legacy Dialogs → Line → Multiple variable means. Two-tailed statistical tests were used, with the significance level set at α = 0.05. A p-value < 0.05 was interpreted as statistically significant, and p < 0.01 was interpreted as highly significant.

Results

Participant flow

A total of 66 symptomatic NA-ICAO patients were assessed, randomized, allocated to the EVT group (n = 32) or conservative medical therapy group (n = 34), all received the assigned treatment, and all completed the 12-month follow-up. The detailed participant flow is presented in Figure 1.

General da...

Discussion

This study demonstrates that EVT for symptomatic NA-ICAO, particularly Hasan Type A/B lesions, can be performed safely and reproducibly when guided by a well-defined, stepwise protocol. The technical success rate of 100% and achievement of TICI 2b-3 reperfusion in all treated patients underscore the feasibility of the procedure in anatomically favorable cases. The absence of loss to follow-up additionally strengthens the reliability of the longitudinal observations. Collectively, these findings support the procedural rob...

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
3.0-Tesla MRI Scanner	GE Healthcare	Discovery MR750w	Preoperative MRA and MRP imaging
Apollo Intracranial Artery Stent System	MicroPort	3.0 mm × 13 mm	Balloon-expandable intracranial stent
Arterial Sheath	Terumo	8F	Femoral artery access sheath
Aspirin Enteric-Coated Tablets	Bayer	100 mg/day	Antiplatelet therapy
Atorvastatin Calcium Tablets	Pfizer	20 mg/day	Lipid-lowering therapy
Clopidogrel Bisulfate Tablets	Sanofi	75 mg/day	Antiplatelet therapy
CT/CTA Scanner	Siemens Healthcare	SOMATOM Definition AS 128-slice	Preoperative CTA and angiography
Disposable Embolic Protection Umbrella	Taijie Weiye Medical	5.0 mm / 6.0 mm	Distal embolic protection during intervention
Drug-Coated Coronary Balloon Dilation Catheter	Medtronic	4.0 mm × 30 mm	Post-dilation to reduce elastic recoil
Hybrid DSA Operating System	(Hospital facility)	Not specified	Real-time fluoroscopic guidance for endovascular procedure
IBM SPSS Statistics	IBM Corp.	Version 26.0	Data processing and statistical analysis
Iodixanol Injection	GE Healthcare	320 mg I/mL, 80–100 mL	Angiographic contrast for DSA
Microguidewire	Asahi Intecc	0.014 inch	Navigation through occluded segment
Neuro RX Intracranial Balloon Dilation Catheter	Medtronic	2.00 mm × 15 mm	Pre-dilation of occluded ICA segment
Neuroform EZ Stent System	Stryker	4.0 mm × 20 mm	Self-expanding intracranial stent
Propofol Injection	AstraZeneca	1% (10 mg/mL)	Induction and maintenance of general anesthesia
Protege RX Tapered Carotid Stent System	Covidien	8–6 mm × 40 mm	Self-expanding carotid stent
Spider FX Embolic Protection Device	Medtronic	5.0 mm / 6.0 mm	Distal embolic protection during intervention