Development and validation of a clinical prediction model for ischemic stroke recurrence after successful stent implantation in symptomatic intracranial atherosclerotic stenosis.

OBJECTIVE: This study aimed to analyze the risk factors for recurrent ischemic stroke in patients with symptomatic intracranial atherosclerotic stenosis (ICAS) who underwent successful stent placement and to establish a nomogram prediction model. METHODS: We utilized data from a prospective collection of 430 consecutive patients at Jining NO.1 People's Hospital from November 2021 to November 2022, conducting further analysis on the subset of 400 patients who met the inclusion criteria. They were further divided into training (n=321) and validation (n=79) groups. In the training group, we used univariate and multivariate COX regression to find independent risk factors for recurrent stroke and then created a nomogram. The assessment of the nomogram's discrimination and calibration was performed through the examination of various measures including the Consistency index (C-index), the area under the receiver operating characteristic (ROC) curves (AUC), and the calibration plots. Decision curve analysis (DCA) was used to evaluate the clinical utility of the nomogram by quantifying the net benefit to the patient under different threshold probabilities. RESULTS: The nomogram for predicting recurrent ischemic stroke in symptomatic ICAS patients after stent placement utilizes six variables: coronary heart disease (CHD), smoking, multiple ICAS, systolic blood pressure (SBP), in-stent restenosis (ISR), and fasting plasma glucose. The C-index (0.884 for the training cohort and 0.87 for the validation cohort) and the time-dependent AUC (>0.7) indicated satisfactory discriminative ability of the nomogram. Furthermore, DCA indicated a clinical net benefit from the nomogram. CONCLUSIONS: The predictive model constructed includes six predictive factors: CHD, smoking, multiple ICAS, SBP, ISR and fasting blood glucose. The model demonstrates good predictive ability and can be utilized to predict ischemic stroke recurrence in patients with symptomatic ICAS after successful stent placement.

Plaque features of the middle cerebral artery are associated with periprocedural complications of intracranial angioplasty and stenting.

PURPOSE: The identification of plaque features in the middle cerebral artery (MCA) may help minimize periprocedural complications and select patients suitable for percutaneous transluminal angioplasty and stenting (PTAS). However, relevant research is lacking. METHODS: We retrospectively included patients with symptomatic MCA stenosis who received PTAS. All patients underwent intracranial vessel wall MRI (VWMRI) before surgery. Periprocedural complications (PC) included ischemic and hemorrhagic stroke within 30 days. Stenosis location, MCA shape, plaque eccentricity and distribution, plaque thickness and length, and enhancement ratio were compared between patients with and without PC. RESULTS: Sixty-six patients were included in the study, of which 12.1% (8/66) had PC. Of the eight patients with PC, seven (87.5%) had superior wall plaques. In the non-PC group (n = 58), nine (17%) patients had superior wall plaques. Compared with patients without PC, those with PC had more frequent superior wall plaques (17% vs 87.5%, p < 0.001) and s-shaped MCAs (19% vs 50%, p = 0.071), different stenosis locations (p = 0.012), thicker plaques (1.58 [1.35, 2.00] vs 1.98 [1.73, 2.43], p = 0.038), and less frequent inferior wall plaques (79.2% vs 12.5%, p < 0.001). Multivariate analysis showed that only the presence of superior wall plaques (OR = 41.54 [2.31, 747.54]) was independently associated with PC. CONCLUSION: MCA plaque features were highly correlated with PC in patients with symptomatic MCA stenosis who underwent PTAS.

Extracranial-Intracranial Bypass and Risk of Stroke and Death in Patients With Symptomatic Artery Occlusion: The CMOSS Randomized Clinical Trial.

Importance: Prior trials of extracranial-intracranial (EC-IC) bypass surgery showed no benefit for stroke prevention in patients with atherosclerotic occlusion of the internal carotid artery (ICA) or middle cerebral artery (MCA), but there have been subsequent improvements in surgical techniques and patient selection. Objective: To evaluate EC-IC bypass surgery in symptomatic patients with atherosclerotic occlusion of the ICA or MCA, using refined patient and operator selection. Design, Setting, and Participants: This was a randomized, open-label, outcome assessor-blinded trial conducted at 13 centers in China. A total of 324 patients with ICA or MCA occlusion with transient ischemic attack or nondisabling ischemic stroke attributed to hemodynamic insufficiency based on computed tomography perfusion imaging were recruited between June 2013 and March 2018 (final follow-up: March 18, 2020). Interventions: EC-IC bypass surgery plus medical therapy (surgical group; n = 161) or medical therapy alone (medical group; n = 163). Medical therapy included antiplatelet therapy and stroke risk factor control. Main Outcomes and Measures: The primary outcome was a composite of stroke or death within 30 days or ipsilateral ischemic stroke beyond 30 days through 2 years after randomization. There were 9 secondary outcomes, including any stroke or death within 2 years and fatal stroke within 2 years. Results: Among 330 patients who were enrolled, 324 patients were confirmed eligible (median age, 52.7 years; 257 men [79.3%]) and 309 (95.4%) completed the trial. For the surgical group vs medical group, no significant difference was found for the composite primary outcome (8.6% [13/151] vs 12.3% [19/155]; incidence difference, -3.6% [95% CI, -10.1% to 2.9%]; hazard ratio [HR], 0.71 [95% CI, 0.33-1.54]; P = .39). The 30-day risk of stroke or death was 6.2% (10/161) in the surgical group and 1.8% (3/163) in the medical group, and the risk of ipsilateral ischemic stroke beyond 30 days through 2 years was 2.0% (3/151) and 10.3% (16/155), respectively. Of the 9 prespecified secondary end points, none showed a significant difference including any stroke or death within 2 years (9.9% [15/152] vs 15.3% [24/157]; incidence difference, -5.4% [95% CI, -12.5% to 1.7%]; HR, 0.69 [95% CI, 0.34-1.39]; P = .30) and fatal stroke within 2 years (2.0% [3/150] vs 0% [0/153]; incidence difference, 1.9% [95% CI, -0.2% to 4.0%]; P = .08). Conclusions and Relevance: Among patients with symptomatic ICA or MCA occlusion and hemodynamic insufficiency, the addition of bypass surgery to medical therapy did not significantly change the risk of the composite outcome of stroke or death within 30 days or ipsilateral ischemic stroke beyond 30 days through 2 years. Trial Registration: ClinicalTrials.gov Identifier: NCT01758614.

Evaluation of safety and efficacy of rapamycin-eluting balloon in patients with intracranial atherosclerotic stenosis: a cohort study.

OBJECTIVE: The safety and efficacy of drug-eluting balloon on the treatment of intracranial atherosclerotic stenosis (ICAS) remain unclear. Here, we present our observation in a cohort study on the safety and efficacy of rapamycin-eluting balloon for patients with ICAS. METHODS: A total of 80 ICAS patients with stenosis degree of 70-99% were included. All patients were treated with rapamycin-eluting balloon and were followed up for 12 months after operation. RESULTS: All patients were successfully treated, where the mean stenosis severity reduced from 85.1 ± 7.6 to 6 ± 4.9%. 8 patients experienced immediate post-operational complications. Two patients passed away during the first month of the follow-up period. Recurrent ischemic syndrome and angiographic restenosis only appeared 7 days after operation. During later follow-up period, none of the patients had clinical angiographic restenosis or needed target vessel revascularization. CONCLUSION: Our data suggest that intracranial stenting with rapamycin-eluting balloon seems to be safe and effective, although more clinical data are needed to support this notion.

Extracranial-Intracranial Cerebral Revascularization for Atherosclerotic Vessel Occlusion: An Updated Systematic Review of the Literature.

BACKGROUND: Atherosclerotic steno-occlusive cerebrovascular disease includes extracranial carotid occlusive and intracranial atherosclerotic disease. Despite the negative findings in Carotid Occlusion Surgery Study (COSS), many large centers continue to report favorable results for revascularization surgery in select groups of patients. The aim of our study was to perform an updated systematic review to investigate the role of revascularization surgery for atherosclerotic steno-occlusive patients in the modern era. METHODS: Five independent reviewers performed Preferred Reporting Items for Systematic Reviews and Meta-Analyses-guided literature searches in October 2022 to identify articles reporting clinical outcomes in adult patients undergoing bypass for atherosclerotic steno-occlusive disease. Primary endpoints used were perioperative and long-term ischemic strokes, intracerebral hemorrhage, bypass patency, and favorable clinical outcomes. Study quality was evaluated with Newcastle-Ottawa, JADAD, and the Oxford Center for Evidence-Based Medicine scales. RESULTS: A total of 6709 articles were identified in the initial search. Of these articles, 50 met the inclusion criteria and were included in the systematic review. A notable increase in the proportion of articles published over the past 10 years was observed. There were 6046 total patients with 4447 bypasses performed over the period from 1978 to 2022. The average length of follow-up was 2.75 ± 2.71 years. The average Newcastle-Ottawa was 6.23 out of 9 stars. There was a significant difference in perioperative stroke (odds ratio [OR], 0.65 [0.48-0.87]; P = 0.004), long-term ischemia (OR, 0.32 [0.23-0.44]; P < 0.0001), overall ischemia (OR, 0.36 [0.28-0.44]; P < 0.0001), and favorable outcomes (OR, 3.63 [2.84-4.64]; P < 0.0001) when comparing pre-COSS to post-COSS time frames in favor of post-COSS. CONCLUSIONS: Based on a systematic review of 50 articles, the existing literature indicates that long-term stroke rates and favorable outcomes for surgical revascularization for steno-occlusive disease have improved over time and are lower than previously reported. Improved patient selection, perioperative care, and surgical techniques may contribute to improved outcomes.

Comparison of drug-coated balloon with conventional balloon for angioplasty in symptomatic intracranial atherosclerotic stenosis.

BACKGROUND: Drug-coated balloon (DCB) angioplasty has been studied for reducing the occurrence of restenosis after treatment for intracranial atherosclerotic stenosis (ICAS), but no comparison has been published of the use of drug-coated and non-coated balloons in angioplasty for ICAS. We aim to compare the safety and efficacy of DCB angioplasty with conventional balloon (CB) angioplasty for the treatment of symptomatic ICAS. METHODS: One hundred cases with symptomatic ICAS treated with DCB (n=49) and CB (n=51) angioplasty were retrospectively analyzed. 1:1 propensity score matching (PSM) was completed to eliminate bias in the patients selected for further analysis. The periprocedural events and follow-up outcomes between the two groups were compared. RESULTS: There were 32 cases in each group after PSM. Technical success (<50% residual stenosis) was achieved in 30 cases (93.8%) in the DCB group and in 28 cases (87.5%) in the CB group. The rates of stroke or mortality within 30 days were 3.1% in the DCB group and 6.3% in the CB group (p=1). The incidence of restenosis in the DCB group (6.3%) was significantly lower than that in the CB group (31.3%) (p=0.01). CONCLUSIONS: Compared with CB angioplasty, DCB angioplasty can effectively reduce the incidence of restenosis. Further studies are needed to validate the role of DCB angioplasty in the management of symptomatic ICAS.

Angiographic tapering sign as a surrogate marker for large vessel occlusion due to intracranial atherosclerotic stenosis and its clinical implication: a retrospective matched case-control study.

BACKGROUND: The purpose of this study was to investigate whether the initial DSA appearance of the occlusion during mechanical thrombectomy (MT) can help distinguish the nature of the underlying lesion and predict radiological and clinical outcomes. METHODS: We retrospectively reviewed cases of patients with acute ischemic stroke who underwent MT for anterior circulation occlusion between March 2017 and February 2020. Underlying intracranial atherosclerotic stenosis (ICAS) was determined based on the presence of fixed stenosis after endovascular treatment. Patients were categorized based on the appearance of the occlusion observed in the initial DSA as tapering sign (+) or (-) groups. We performed 1:2 propensity score matching to establish a proper control group among the tapering sign (-) group. We analyzed and compared baseline characteristics and clinical outcomes between the two groups. RESULTS: A total of 293 patients (tapering sign (+), n=47; tapering sign (-), n=246) were included in the analysis. The procedure time of MT was significantly longer for the tapering sign (+) group, and the successful recanalization rate after MT was significantly lower in the tapering sign (+) group than in the tapering sign (-) group. Logistic regression showed that ICAS-related occlusion was strongly associated with a positive angiographic tapering sign, and the angiographic tapering sign was a negative factor for the first-pass effect during MT. However, a 3-month good functional outcome was not significantly associated with the angiographic tapering sign. CONCLUSIONS: The tapering sign on the initial DSA could be a surrogate marker for ICAS-related occlusion and procedural difficulty. However, its clinical significance remains unclear.

Baseline vessel wall magnetic resonance imaging characteristics associated with in-stent restenosis for intracranial atherosclerotic stenosis.

BACKGROUND: Imaging factors, specifically baseline plaque features on high-resolution magnetic resonance vessel wall imaging (HR-VWI) that could be associated with in-stent restenosis (ISR), are still unknown. We aimed to investigate the presenting clinical and plaque features on HR-VWI associated with ISR. METHODS: Sixty-four patients with intracranial stent placement for intracranial atherosclerotic stenosis who had pre- and post-contrast T1-weighted HR-VWI on 3.0T prior to stenting were included in this analysis. Student's t-test, Mann-Whitney U test, χ2 test, or the Cochran-Mantel-Haenszel (CMH) test were used to compare clinical and baseline HR-VWI characteristics of the patients between the ISR and non-ISR groups. Univariable and multivariable logistic analysis were used to test the clinical and imaging factors associated with ISR. RESULTS: Among the 64 patients, 9 patients (14.06%) developed ISR during the 2-year follow-up period. Plaque burden (median 0.89 vs 0.92, P=0.04), minimum lumen area (0.009 cm2 vs 0.006 cm2, P=0.04), plaque eccentricity (55.6% vs 89.1%, P＜0.01), enhancement ratio (1.36 vs 0.84, P＜0.01), and enhancement involvement (type 2 represents ≥50% cross-sectional wall involvement; 100% vs 63.6%, P=0.03) all significantly differed between patients with and without ISR. Multivariable analysis revealed that lower frequency of plaque eccentricity (OR 0.18, 95% CI 0.04 to 0.96, P=0.04) and higher enhancement ratio (OR 3.57, 95% CI 1.02 to 12.48, P=0.04) were independently associated with ISR. CONCLUSIONS: Preliminary findings showed that ISR was independently associated with plaque concentricity and higher enhancement ratios on pre-stenting HR-VWI for patients with symptomatic intracranial atherosclerotic stenosis.

Safety and efficacy of drug coated balloon angioplasty for intracranial atherosclerotic disease.

BACKGROUND: Drug coated balloon (DCB) angioplasty can provide sustained anti-restenotic efficacy without the limitations of permanent vascular implantation and is presumably ideal for treating intracranial atherosclerotic disease. However, the safety of paclitaxel in the neurovasculature remains a concern. METHODS: 242 patients with angiographically verified symptomatic stenosis >70% in intracranial arteries treated with DCB angioplasty were reviewed divided into two groups: group A, patients with stenotic intracranial arteries; and group B, patients with acute, subacute, or chronic occluded intracranial arteries. The primary endpoint was any stroke or death within 30 days. The secondary endpoint was arterial restenosis of >50% during follow-up. RESULTS: 16 major and 12 minor complications occurred among 245 procedures (6.5% and 4.9%, respectively). Five patients died within 30 days after the procedure (2.1%, 5/242). 12 major and 12 minor complications occurred among 211 procedures in group A (5.7% and 5.7%). In group B, four major complications occurred among 34 procedures (11.8%). Hyperperfusion and perforator stroke accounted for half of all complications (53.6%, 15/28). Restenosis >50% was present in eight lesions during the follow-up period (4.8%, 8/167). CONCLUSIONS: After treatment with DCB angioplasty, complications were no different from those after standard balloon angioplasty or stenting. This study suggests that DCB angioplasty may be a safe and effective procedure for intracranial arterial stenosis.

Modern Appraisal of Patency and Complications in Cerebral Bypass Surgery: A Single Institution Experience.

BACKGROUND: Cerebral bypass is a valuable surgical technique in well-selected patient populations. Updated clinical guidelines and improved surgical techniques warrant a contemporary reevaluation of the complications and patency to inform clinical practice and enhance postoperative patient care. OBJECTIVE: To assess the complication rates and postoperative graft patency for the 3 most common indications for bypass surgery: moyamoya disease, intracranial atherosclerosis, and intracranial aneurysms. METHODS: Perioperative notes of 175 consecutive bypass patients at a single institution were retrospectively identified to evaluate the clinical course and complications of surgery. RESULTS: The rate of total postoperative complications between moyamoya disease (9 of 98, 9.2%), intracranial atherosclerotic disease (7 of 57, 12.3%), and intracranial aneurysm (4 of 20, 20%) was not statistically different (P = .33). Immediate postoperative bypass patency was significantly higher in moyamoya disease (90 of 96, 93.8%) and intracranial atherosclerotic disease (48 of 51, 94.1%) than in intracranial aneurysm (13 of 18, 72.2%; P = .02). Intravenous heparin administration during bypass suturing was negatively associated with immediate postoperative patency (87% heparin patency vs 99% no heparin patency; P = .02). Double-barrel bypass trended toward an increased risk of wound healing complications (2 of 13, 15.4%) compared with the single-barrel bypass technique (4 of 156, 2.6%; P = .07). CONCLUSION: Cerebral bypass surgery remains an excellent surgical treatment for moyamoya disease, intracranial atherosclerosis, and intracranial aneurysms. This study suggests bypass is safer in moyamoya disease and intracranial atherosclerosis. Additional studies to clarify the risk of single-barrel vs double-barrel bypass and intraoperative heparin-stratified complications may be beneficial.

Cost-Effectiveness Analysis of Encephaloduroarteriosynangiosis Surgery for Symptomatic Intracranial Atherosclerotic Disease.

Encephaloduroarteriosynangiosis (EDAS) is a promising treatment for cerebral arterial steno-occlusive disorders, with proven efficacy in moyamoya disease and a growing interest in potential application for patients with symptomatic intracranial atherosclerotic disease, given the early results of intermediate development trials showing reduced rates of recurrence stroke and improved clinical outcomes compared with those patients treated with intense medical management (IMM) alone. Although clinical outcomes are the fundamental goal when considering patient care paradigms, a cost-effective analysis is key to obtaining a comprehensive understanding of the impact EDAS may provide to patients with atherosclerotic disease on a larger scale. Here, we evaluate the EDAS + IMM cost-effectiveness over time in the treatment of intracranial atherosclerotic disease compared with IMM alone.

Association of residual stenosis after balloon angioplasty with vessel wall geometries in intracranial atherosclerosis.

BACKGROUND: Percutaneous transluminal balloon angioplasty (PTBA) may be an alternative treatment for patients with symptomatic intracranial atherosclerotic disease (ICAD) refractory to medical treatment. This study aimed to investigate the association of vessel wall geometric characteristics on high-resolution magnetic resonance vessel wall imaging (MR-VWI) with low residual stenosis in patients with ICAD after PTBA. METHODS: Patients with symptomatic ICAD who underwent PTBA were prospectively and consecutively enrolled. High-resolution MR-VWI was performed before the PTBA. Vessel wall geometries of the target artery, including normalized wall index (NWI: wall area/vessel area × 100%), normalized wall thickness index (NWTI: mean wall thickness/vessel radius × 100%), and remodeling index (RI) were evaluated. Low residual stenosis was defined as postprocedural stenosis degree ≤50%. Perioperative complications including symptomatic ischemic stroke/intracranial hemorrhage, death, and arterial dissection were recorded. The baseline characteristics, vessel wall geometries, and perioperative complications were compared between the patients with low residual stenosis and high residual stenosis. RESULTS: Among 60 patients prospectively enrolled, low residual stenosis was achieved in 46 participants (77%). Three patients (5%) suffered from symptomatic ischemic stroke within 30 days. Multivariable logistic regression showed that a lower NWI and lower NWTI were associated with low residual stenosis after PTBA (adjusted OR 0.57, 95% CI 0.35 to 0.94, p=0.027; and adjusted OR 0.88, 95% CI 0.80 to 0.98, p=0.015). CONCLUSIONS: Lower NWI and NWTI of the target artery on high-resolution MR-VWI were associated with low residual stenosis in patients with ICAD after PTBA.

Safety and efficacy of balloon-mounted stent in the treatment of symptomatic intracranial atherosclerotic disease: a multicenter experience.

BACKGROUND: Randomized clinical trials have failed to prove that the safety and efficacy of endovascular treatment for symptomatic intracranial atherosclerotic disease (ICAD) is better than that of medical management. A recent study using a self-expandable stent showed acceptable lower rates of periprocedural complications. OBJECTIVE: To study the safety and efficacy of a balloon-mounted stent (BMS) in the treatment of symptomatic ICAD. METHODS: Prospectively maintained databases from 15 neuroendovascular centers between 2010 and 2020 were reviewed. Patients were included if they had severe symptomatic intracranial stenosis in the target artery, medical management had failed, and they underwent intracranial stenting with BMS after 24 hours of the qualifying event. The primary outcome was the occurrence of stroke and mortality within 72 hours after the procedure. Secondary outcomes were the occurrence of stroke, transient ischemic attacks (TIAs), and mortality on long-term follow-up. RESULTS: A total of 232 patients were eligible for the analysis (mean age 62.8 years, 34.1% female). The intracranial stenotic lesions were located in the anterior circulation in 135 (58.2%) cases. Recurrent stroke was the qualifying event in 165 (71.1%) while recurrent TIA was identified in 67 (28.9%) cases. The median (IQR) time from the qualifying event to stenting was 5 (2-20.75) days. Strokes were reported in 13 (5.6%) patients within 72 hours of the procedure; 9 (3.9%) ischemic and 4 (1.7%) hemorrhagic, and mortality in 2 (0.9%) cases. Among 189 patients with median follow-up time 6 (3-14.5) months, 12 (6.3%) had TIA and 7 (3.7%) had strokes. Three patients (1.6%) died from causes not related to stroke. CONCLUSION: Our study has shown that BMS may be a safe and effective treatment for medically refractory symptomatic ICAD. Additional prospective randomized clinical trials are warranted.

Increased incidence and treatment of intracranial atherosclerotic disease during mechanical thrombectomy is safe, even with an increased number of passes.

BACKGROUND: The incidence of intracranial atherosclerotic disease (ICAD) in acute ischemic stroke treated with mechanical thrombectomy (MT) is not well defined, and its description may lead to improved stroke devices and rates of first pass success. METHODS: A retrospective study was performed on MT patients from 2012 to 2019 at a comprehensive stroke center using chart review and angiogram analysis. Angiograms at the time of MT were reviewed for ICAD, and location and severity were recorded. Patients with ICAD were divided according to ICAD location relative to the large vessel occlusion (LVO) site. Statistical analyses were performed on baseline demographics, comorbidities, MT procedure variables, outcome variables, and their association with ICAD. RESULTS: Of the 533 patients (mean age 70.4 (SD 13.20) years, 43.5% women), 131 (24.6%) had ICAD. There was no significant difference in favorable discharge outcomes (modified Rankin Scale score of 0-2; 23.8% ICAD vs 27.0% non-ICAD; p=0.82) or groin puncture to recanalization times (average 43.5 (range 8-181) min for ICAD vs 40.2 (4-204) min for non-ICAD; p=0.42). Patients with ICAD experienced a significantly higher number of passes (average 1.8 (range 1-7) passes for ICAD vs 1.6 (1-5) passes for non-ICAD; p=0.0059). Adjusting for age, ≥3 device passes, baseline National Institutes of Health Stroke Scale, rates of angioplasty only, rates of concurrent angioplasty and stenting, coronary artery disease and atrial fibrillation incidences, and time from emergency department arrival to recanalization, yielded no significant difference in rates of favorable outcomes between the two groups. CONCLUSION: Patients who underwent MT with underlying ICAD had similar rates of favorable outcomes as those without, but required a higher number of device passes.