Recurrent Cerebral Ischemic Events Research Articles

Study protocol for LOMCAD Trial: Effect of lomerizine hydrochloride to prevent recurrence of cerebral ischemic events in CADASIL patients

ObjectivesCerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is one of the most common monogenic cerebral small vessel diseases. Our previous observational study suggested that lomerizine hydrochloride, a calcium channel blocker approved in Japan in 1999 for the prevention of migraine headaches, is also effective for preventing recurrent ischemic stroke in CADASIL patients. The aim of this study (LOMCAD trial) is to verify the efficacy of lomerizine hydrochloride. Materials and MethodsThis is a multicenter, prospective, single-arm trial, using a historical control for comparison. CADASIL patients with a history of two or more cerebral ischemic events within the last two years will be administered lomerizine hydrochloride (5-mg tablet twice daily) for 24 months. The primary endpoint is symptomatic cerebral ischemic events during the 24-month period. Using our historical data and Bayesian sample size calculation based on a prior predictive distribution, the planned sample size was determined as 20 subjects. ConclusionWe have planned a clinical trial to verify the effectiveness of lomerizine hydrochloride as prophylaxis to prevent recurrent cerebral ischemic events in CADASIL patients. RegistrationThe LOMCAD trial has been registered in the Japan Registry of Clinical Trials (jRCTs051220072, https://jrct.niph.go.jp/latest-detail/jRCTs051220072).

Clinical characteristics and efficacy analysis of various treatments for spontaneous carotid artery dissection

Objective: To investigate the clinical features of spontaneous carotid artery dissection (SCAD) and the efficacy of different treatment methods. Methods: The clinical data of 164 patients with SCAD who were treated at the First Affiliated Hospital of Zhengzhou University from June 2018 to January 2023 were retrospectively analyzed. There were 127 males and 37 females, with a mean age of (49.5±11.1) years. They were divided into conservative treatment group (n=100) and surgical treatment group (n=64) according to whether they received surgical treatment. Patients were followed at 3, 6, and 12 months after discharge and annually thereafter through outpatient or inpatient visits. The incidence of cerebral ischemic events, cerebral hemorrhage events, and mortality rates during hospitalization and follow-up periods were analyzed in the two patient groups. To examine correlates of revascularization in SCAD, multifactorial logistic regression analysis was used. Results: Of the 164 patients, 18 patients had bilateral SCAD and a total of 182 carotid arteries were included in the study. Ischemic stroke (85 cases, 51.8%) and transient ischemic attack (31 cases, 18.9%) were the main clinical manifestations in SCAD patients. Hypertension (81 cases, 49.4%) and hyperlipidemia (39 cases, 23.8%) were the main comorbidities in SCAD patients. During hospitalization, 100 patients in the conservative treatment group received medication in 113 carotid arteries, no new cerebral ischemic events or symptomatic intracranial hemorrhage events occurred, and no death occurred. A total of 69 carotid arteries were surgically treated in 64 patients in the surgical treatment group. The success rate was 97.1% (67/69). In the surgical treatment group, the proportion of carotid stenosis degree≥90% was 47.8% (33/69), the proportion of type Ⅱ SCAD was 60.9% (42/69), and the proportion discharged from the hospital to receive antiplatelet therapy was 92.8% (64/69), which were higher than those in the conservative treatment group, which were 25.7% (29/113), 45.1% (51/113), and 73.5% (83/113), respectively (all P<0.05). The follow-up time [M(Q1, Q3)] in the conservative treatment group was 24 (13, 34) months, with an 8% (9/113) rate of ischemic events and a 7.1% (8/113) rate of readmission; in the surgical treatment group, the follow-up time was 24 (11, 38) months, and there were no new ischemic events or deaths. The results of multifactorial logistic regression analysis showed that the degree of true luminal stenosis<90% (OR=2.738, 95%CI: 1.067-7.026, P=0.036) and type Ⅰ dissections (OR=2.656, 95%CI: 1.189-5.935, P=0.017) were the correlates of complete revascularization. Conclusions: Ischemic stroke and transient ischemic attack are the main clinical manifestations in patients with SCAD. Pharmacological antithrombotic therapy remains the method of choice, and endovascular treatment after failure of conservative therapy reduces the risk of recurrent long-term cerebral ischemic events and the re-admission rate of patients.

Endovascular re-canalization for symptomatic non-acute intracranial large artery occlusion: a single-center retrospective study.

Managing patients with symptomatic non-acute intracranial large artery occlusion (SNA-ILAO) poses a significant challenge due to the high morbidity and risk of recurrent critical ischemic events, even with standard medical therapy. This unique subgroup of patients requires specialized attention. The aim of this study is to evaluate the feasibility and safety of endovascular interventional recanalization for SNA-ILAO. We retrospectively collected data of patients with SNA-ILAO who underwent endovascular interventional therapy at the Fourth Affiliated Hospital of Xinjiang Medical University from 2018 to 2021. The collected data included clinical demography, imaging data, treatment details, and prognosis. Follow-up imaging assessments were conducted for the patients, and descriptive statistics were performed. A total of 24 patients were enrolled, with a majority being male (58.3%) and a mean age of 62.0±9.3 years. The pre-treatment median modified Rankin scale (mRS) and the National Institutes of Health Stroke Scale (NIHSS) scores at baseline were 3 and 1, respectively. The most common occlusion location was the middle cerebral artery (MCA), including M1 (70.8%), M2 (20.8%), and M3 (4.7%). Successful recanalization was achieved in all 24 patients, with 21 cases (87.5%) achieving thrombolysis in cerebral infarction (TICI) 3 reperfusion and the remaining 3 cases (12.5%) achieving TICI 2b reperfusion. Asymptomatic intracranial hemorrhage (ICH) occurred in 2 patients (8.3%). During the first 30-day clinical follow-up, none of these patients experienced any recurrent cerebral ischemic events. During the 29.5-month follow-up period for vessel imaging, only 12.5% (3/24) of patients who had follow-up imaging experienced re-stenosis. Endovascular recanalization is a potentially safe and effective procedure for patients with SNA-ILAO. However, it is important to note that there is still a non-negligible rate of complications associated with this treatment. Therefore, exercising caution and implementing strict controls when administering this procedure is crucial.

Role of Cardiac Risk Scores in Clinical Use to Predict Outcomes of Acute Ischemic Stroke.

Acute coronary syndromes and ischemic stroke have similar risk factors. Risk scores help to identify disease severity in both diseases. We aimed to evaluate if HEART (History, ECG, Age, Risk factors, and Troponin) score could predict re-hospitalization, recurrent cardiac/cerebrovascular events risk, and mortality within 1-year follow-up in patients presenting with acute ischemic stroke. Patients hospitalized with a diagnosis of acute ischemic stroke in our tertiary center between 2019 and 2021 were included in this retrospective study. CHA2DS2-VASc and HEART scores on admission were calculated. In-hospital, 1-month, and 1-year mortalities, as well as re-hospitalization due to recurrent ischemic (cardiac/cerebral), were defined as major adverse cardiac and cerebrovascular events (MACCE), and occurrence of MACCE was accepted as the primary endpoint of the study. Comparative statistical and regression analyses were obtained. A total of 297 patients were included. The mortality rate for 30 days was 7.4% and 1 year was 20.5%. HEART and CHA2DS2-VASc scores were found independent risk factors associated with the occurrence of MACCE. Patients who experienced MACCE had higher HEART and CHA2DS2-VASc scores. Meanwhile, HEART score had better prognostic accuracy than CHA2DS2-VASc score when a cutoff value of 3.5 was set, which is associated with 84.7% sensitivity and 75.2% specificity in the prediction of MACCE. HEART score is effective in determining re-hospitalization and recurrent cerebral ischemic event risk as well as mortality within 30 days and 1 year in patients presenting with acute ischemic stroke. Thus, concomitant use of HEART and CHA2DS2-VASc scores may provide better characterization of worse prognosis in ischemic stroke patients with high sensitivity and specificity.

Risk of new cerebral ischemic events in patients with symptomatic internal carotid artery stenosis while awaiting carotid stent placement.

Although there is an emphasis on performing carotid artery stent (CAS) placement within 2weeks after index event of transient ischemic attack (TIA) or minor stroke in patients with significant extracranial internal carotid artery (ICA) stenosis, the risks and characteristics of recurrent cerebral ischemic event while waiting for CAS placement are not well defined. We analyzed patients admitted to our institution over a 45-month period with symptomatic extracranial ICA stenosis. We identified any new cerebral ischemic events that occurred between index cerebral or retinal ischemic event and CAS placement and categorized them as TIA and minor or major ischemic strokes. We calculated the risk of new ipsilateral cerebral ischemic events between index cerebral or retinal ischemic event and CAS placement. The mean age of 131 patients analyzed was 67years (range: 47-94 years; 92 were men), and 94 and 37 patients had 70%-99% and 50%-69% severity of stenosis, respectively. The mean and median time intervals between index cerebral or retinal ischemic event and CAS performance were 28 (standard deviation [SD] 30) and 7 (interquartile range 33) days, respectively. A total of 9 of 131 patients (6.9%, 95% confidence interval 2.5%-11.2%) experienced new cerebral ischemic events over 3637 patient days of observation. The risk of new ipsilateral cerebral ischemic events was 2.5 per 1000 patient days of observation. We estimated the risk of new ipsilateral cerebral ischemic events in patients with ICA stenosis ≥50% in severity while waiting for CAS placement to guide appropriate timing of procedure.

Patent foramen ovale closure in non-elderly and elderly patients with cryptogenic stroke: a hospital-based cohort study.

The efficacy of patent foramen ovale (PFO) closure in the elderly population is unclear. We aimed to investigate the efficacy and safety of PFO closure in non-elderly and elderly patients. Patients over 18 years of age with cryptogenic stroke (CS) or transient ischemic attack and PFO were prospectively enrolled and classified into two groups according to treatment: (1) closure of PFO (the PFOC group) and (2) medical treatment alone (the non-PFOC group). The primary outcome was a composite of recurrent cerebral ischemic events and all-cause mortality during the follow-up period. A modified Ranking Scale [mRS] at 180 days was recorded. The safety outcomes were procedure-related adverse events and periprocedural atrial fibrillation. The results between the PFOC and non-PFOC groups in non-elderly (<60 years) and elderly (≥60 years) patients were compared. We enrolled 173 patients, 78 (45%) of whom were elderly. During a mean follow-up of 2.5 years, the incidence of primary outcome was significantly lower in the PFOC group (6.2% vs. 17.1%, hazard ratio[HR] = 0.35, 95% CI 0.13-0.97, p = 0.043) in adjusted Cox regression analysis. Compared with the non-PFOC group, the PFOC group had a numerically lower risk of the primary outcome in both the elderly (HR 0.26, 95% CI 0.07-1.01, p = 0.051) and the non-elderly (HR 0.61, 95% CI 0.11-3.27, p = 0.574) groups. In addition, patients with PFO closure in the elderly group had a lower median mRS at 180 days (p = 0.002). The rate of safety outcome was similar between the non-elderly and elderly groups. PFO closure was associated with a reduced risk of the primary outcome in patients with PFO and CS in our total cohort, which included non-elderly and elderly patients. Compared to those without PFO closure, elderly patients with PFO closure had a better functional outcome at 180 days. PFO closure might be considered in selected elderly patients with PFO.

Stroke recurrence is associated with unfavorable intracranial venous outflow in patients with symptomatic intracranial atherosclerotic large vessel severe stenosis or occlusion.

The purpose of this study was to investigate the predictive value of intracranial venous outflow for recurrent cerebral ischemic events (RCIE) in patients with symptomatic intracranial atherosclerotic large-vessel severe stenosis or occlusion (sICAS-S/O). This retrospective study included sICAS-S/O patients with anterior circulation who underwent dynamic computed tomography angiography (dCTA) and computed tomography perfusion (CTP). Arterial collaterals were evaluated using the pial arterial filling score for dCTA data, tissue-level collaterals (TLC) were assessed using the high-perfusion intensity ratio (HIR, Tmax >10 s/Tmax >6 s), and cortical veins were evaluated using the multi-phase venous score (MVS) for the vein of Labbé (VOL), sphenoparietal sinus (SPS), and superficial cerebral middle vein (SCMV). The relationships between multi-phase venous outflow (mVO), TLC, and 1-year RCIE were analyzed. Ninety-nine patients were included, 37 of whom had unfavorable mVO (mVO-) and 62 of whom had favorable mVO (mVO+). Compared with the mVO+ patients, mVO- patients had a higher admission National Institutes of Health Stroke Scale (NIHSS) score (median, 4 [interquartile range (IQR), 0-9] vs. 1 [IQR, 0-4]; p = 0.048), larger ischemic volume (median, 74.3 [IQR, 10.1-177.9] vs. 20.9 [IQR, 5-86.4] mL; p = 0.042), and worse tissue perfusion (median, 0.04 [IQR, 0-0.17] vs. 0 [IQR, 0-0.03]; p = 0.007). Multivariate regression analysis showed that mVO- was an independent predictor of 1-year RCIE. For patients with sICAS-S/O of the anterior circulation, unfavorable intracranial venous outflow is a potential imaging indicator for predicting higher 1-year RCIE risk.

Abstract WP142: Risk Of New Ischemic Events In Patients With Symptomatic Internal Carotid Artery Stenosis While Awaiting Carotid Artery Stent Placement

Introduction: Although there is emphasis on performing carotid artery stent placement (CAS) within two weeks after index event of transient ischemic attack (TIA) or minor stroke in patients with cervical internal carotid artery (ICA) stenosis, the risk and characteristics of recurrent cerebral ischemic events while waiting for CAS are not well defined. Method: We analyzed patients admitted to our institution over a 45-month period with symptomatic cervical ICA stenosis. All patients were initiated on daily aspirin and clopidogrel 75mg on the day of admission. We identified any new cerebral ischemic events that occurred between index event and CAS and categorized them as TIA, and minor or major ischemic strokes. We calculated the risk of new ipsilateral cerebral ischemic events between index ischemic event and CAS. Results: The mean age of 150 patients analyzed was 67 years (range: 46-94 years; 106 were men); and 94 and 56 patients had ≥ 70% and 50-69% stenosis, respectively. The mean and median time intervals between index event and CAS performance were 25 and 6 days, respectively. A total of 6 new cerebral ischemic events (5 TIAs and 1 major stroke) were observed over 3,776 patient days of observation. The risk of new ipsilateral cerebral ischemic events between index ischemic event and CAS performance was 1.6 per 1000 patient days of observation. Conclucion: We identified a low risk of new ipsilateral cerebral ischemic events in patients with ≥ 50% ICA stenosis while waiting for CAS presumably due to early initiation of dual antiplatelets.

Cryptogenic ischemic cerebral vascular disease with patent foramen ovale: analysis of the long-term efficacy of treatments and prognostic factors

Objective: To evaluate the long-term efficacy of treatments on cryptogenic ischemic cerebral vascular disease (CICVD) with patent foramen ovale (PFO) and analyze prognostic factors, so as to provide the references for the treatment and secondary prevention of PFO related cerebral vascular disease. Methods: Consecutive patients with CICVD and PFO related right-to-left shunting confirmed by transesophageal echocardiography or transcranial doppler bubble test, who admitted to the Department of Neurology in Xuanwu Hospital from May 1, 2012 to December 31 2021 were enrolled. All the patients underwent hypercoagulability screening, and the degree of hypercoagulability was evaluated by a scoring scale. Each PFO was classified as either high-risk or low-risk according to its anatomic features. Patients were divided into the drug treatment group (including antiplatelet and anticoagulation therapies) and transcatheter PFO closure group. After follow-up, the recurrence of cerebral ischemic events were compared between the two groups by Kaplan-Meier method, the prognostic factors were analyzed by multifactorial Cox's regression model. Results: A total of 117 patients were recruited, 10 patients were lost to follow-up, and 107 patients were included in the final analysis, consisting of 66 males and 41 females, with age ranging from 14 to 67 years and the follow-up period of 1 229 (45, 3 508) d. The recurrence rate of cerebral ischemic events was 6% (4/66) and 7% (3/41) for the drug treatment group (66 cases) and closure group (41 cases), respectively, and residual shunting was detected in all patients with recurrent events in the closure group. Cumulative hazard curve indicated that there was no significant difference of recurrence risk of cerebral ischemic events between the two groups (cumulative recurrence rate: 17.9% in the closure group vs 7.1% in the drug treatment group, χ2=0.368, P=0.544), and the insignificance persisted even in subgroup analysis of CICVD patients with either high-risk (χ2=0.685, P=0.408) or low-risk PFO (χ2=0.072, P=0.789). Cox's regression model indicated that hypercoagulability related factor score was an independent predictor of recurrent cerebral ischemic events (HR=2.079, 95%CI 1.069-4.045, P=0.031) after adjusting for high-risk PFO, PFO closure and other confounding factors. Moreover, a rising trend of cumulative recurrence rate was observed as the score got higher (P=0.046). Conclusions: For CICVD patients with either high-risk or low-risk PFO, the significant value of drug treatment as the first-line therapy for PFO related CICVD should not be ignored, which awaits further discussion. The abnormality of hypercoagulability related factors might increase the recurrent risk of cerebral ischemic events, which calls for more attention and should be screened and treated with corresponding medication.

Abstract 9226: Stroke in Bicuspid Aortic Valve

Background: The bicuspid aortic valve (BAV) exhibits abnormal geometry and transvalvular flow and is susceptible to calcification with subsequent cardioembolic stroke from calcific embolic material. However, the description of embolic ischemic strokes in patients with BAV is limited to case reports. Methods: Consecutive patients from 1975-2015 with BAV (n=5401) at our institution were retrospectively identified. Patients with ischemic stroke before aortic valve replacement (AVR) were analyzed, and the stroke was characterized. Patients were grouped according to stroke etiology: calcific embolism from a BAV (BAV stroke); large artery atherosclerotic or lacunar stroke (LA stroke); and non-BAV, non-large artery embolic stroke (nLA stroke). Results: There were 83/5401 (1.5%) patients with ischemic stroke. Mean age was 54 ± 12 years and 28% were female. Stroke etiology was BAV stroke in 26/83 (31%), LA stroke in 23/83 (28%), nLA stroke in 30/83 (36%), and other in 4/83 (5%). Stroke was embolic in 72/83 (87%), as shown in Figure 1. CHA 2 DS 2 -VASc score was not different in patients with BAV stroke (1.4 ± 1.2) versus nLA stroke (1.8 ± 1.2, p=0.188) but was higher in LA stroke (2.3 ± 1.2, p=0.005 vs. BAV stroke). Recurrent stroke occurred in 41% overall (50% BAV stroke vs. 30% LA stroke vs. 47% nLA stroke, both p=NS vs. BAV stroke). BAV stroke was more commonly located in the retinal circulation (39% BAV stroke vs. 13% LA stroke [p=0.044] vs. 0% nLA stroke [p=0.002]). Patients with BAV and LA stroke were more likely to have moderate-to-severe aortic stenosis and undergo AVR sooner after stroke compared to patients with nLA stroke. Conclusions: Stroke is an important complication in patients with BAV. The most common type of stroke in BAV is embolic. Greater than one-third of embolic stroke resulted from embolism from a calcific aortic valve. Patients with BAV stroke commonly have a history of recurrent cerebral ischemic events, severe valvular disease, and proceed to AVR soon after stroke.

Preoperative antithrombotic treatment in acutely symptomatic carotid artery stenosis

ObjectivesEarly recurrence of cerebral ischemia in acutely symptomatic carotid artery stenosis can precede revascularization. The optimal antithrombotic regimen for this high-risk population is not well established. Although antiplatelet agents are commonly used, there is limited evidence for the use of anticoagulants. We sought to understand the safety and efficacy of short-term preoperative anticoagulants in secondary prevention of recurrent cerebral ischemic events from acutely symptomatic carotid stenosis in patients awaiting carotid endarterectomy (CEA). Materials and MethodsA retrospective query of a prospective single institution registry of carotid revascularization was performed. Patients who presented with acute ischemic stroke or transient ischemic attack (TIA) attributable to an ipsilateral internal carotid artery stenosis (ICA) were included. Antiplatelet (AP) only and anticoagulation (AC) treatment arms were compared. The primary outcome was a composite of preoperative recurrent ischemic stroke or TIA. The primary safety outcome was symptomatic intracranial hemorrhage. ResultsOut of 443 CEA patients, 342 were in the AC group and 101 in the AP group. Baseline characteristics between groups (AC vs AP) were similar apart from age (71±10.5 vs 73±9.5, p=0.04), premorbid modified Rankin scale (mRS) score (1.0±1.2 vs 1.4±1.3, p=0.03) and stroke as presenting symptom (65.8 vs 53.5%, p=0.02). Patients in the AC group had a lower incidence of recurrent stroke/TIA (3.8 vs 10.9%, p=0.006). One patient had symptomatic intracranial hemorrhage in the AC group, and none in the AP group. In multivariate analysis controlling for age, premorbid mRS, stroke severity, degree of stenosis, presence of intraluminal thrombus (ILT) and time to surgery, AC was protective (OR 0.30, p=0.007). This effect persisted in the cohort exclusively without ILT (OR 0.23, p=0.002). ConclusionsShort term preoperative anticoagulation in patients with acutely symptomatic carotid stenosis appears safe and effective compared to antiplatelet agents alone in the prevention of recurrent cerebral ischemic events while awaiting CEA.

Balloon expandable Stent utility for early Secondary Prevention of new Cerebral Ischemic events Caused by Intracranial Atherosclerotic Stenosis. Technical Nuances

Objective: Recurrent cerebral ischemic events are estimated to appear in between 12-15% of symptomatic intracranial atherosclerotic disease (ICAD), regardless of the use of leading pharmacological therapies. Balloon expandable stent (balloon mounted coronary stent) could represent a feasible alternative in this disease’s treatment. This study pretends to report the balloon-expandable placement experience in our center. Materials and Methods: A unicentric retrospective study dated between September 2009 and March 2018 was conducted. Patients previously diagnosed with ICAD and symptomatic stenosis treated with balloon-expandable stent were included. Clinical features, morbidity, mortality, short and long-term evolution, and pre-and post-treatment angiographic features were analyzed, as well as a mean 8 years-period follow-up. Data are presented as means, frequencies, and percentages for categorical variables, and ranks for continuous variables. Statistical analysis was carried by IBM SPSS Statistics Base V22.0 (IBM Corporation, Mexico). A Wilcoxon Signed-rank test statistical analysis was performed. Statistical significance was considered when a p-value lesser than 0.05 was measured for every result. Results: A total of 6 patients with 7 affected vessels were treated, with an average age of 62.7 years. Affected and treated vessels were located in the Internal Carotid Artery (ICA) segment in 42.9%, Vertebral Artery (VA) V4 segment in 14.3%, Middle Cerebral Artery (MCA) M1 segment in 28.5%, and Posterior Cerebral Artery (PCA) P1 segment in 14.3%. The incidence of peri-operatory thrombotic events was 0%. Intracranial hemorrhage presented in 0% of cases. Recurrent ischemic or thrombotic events were not reported in a 97-months mean follow-up. 71.4% of patients scored ≤2 in the modified Rankin Score (mRS) pre-treatment, in a 90 day and 12-month follow-up. 100% presented a favorable evolution with mRS ≤2. Restenosis cases were not reported in radiologic control and retreatment was not needed in a 97-month mean follow-up. Conclusions: This study suggests that balloon-expandable stent therapy with some technical endovascular variants for its navigation and placement could be a safe and effective alternative in the treatment of ICAD as a means of cerebral ischemic event early secondary prevention. We propose to consider not to limit endovascular treatment exclusively to those symptomatic ICAD patients refractory to medical-exclusive treatment, as a means to reduce the risk of presenting a new neurological deficit. Further expanded clinical trials are needed to confirm these findings and the advantage of this kind of stents against other kinds reported in the literature.

Stroke Recurrence in First-Ever Symptomatic Carotid Web: A Cohort Study

A multicenter, observational cohort study was performed from January 2008 to March 2019. A total of 92 consecutive Afro-Caribbean patients (57% women; mean age, 50 years) had first-ever ipsilateral cerebral ischemic events (79 ischemic strokes; 13 transient ischemic attacks) associated with an ipsilateral carotid artery web diagnosed by computed tomography angiography. The mean symptomatic bulb stenosis was only 36%. During a mean follow-up of 4 years, 21% (19 of 92) of patients experienced recurrent ipsilateral cerebral ischemic events (16 strokes; 3 transient ischemic attacks). Of 21 patients who underwent carotid endarterectomy and two who underwent carotid artery stenting (CAS), no recurrence occurred during a median follow-up of 3 years. Using medical treatment alone, the cumulative recurrent cerebral ischemic event rate was 20% at 2 years and 27% at 5 years. Using medical treatment alone, symptomatic carotid artery webs were associated with a high rate of recurrence that reached 27% at 5 years. Surgery or stenting seems to be efficient.

Endovascular revascularization of chronically occluded vertebral artery: single-center experience.

IntroductionChronic vertebral basilar artery occlusion is one of the most common causes of ischemic stroke, which accounts for roughly 20% of all cases. However, the evidence for the precise clinical effect in treatment of the initial segment of chronic vertebral basilar artery occlusion is not sufficient.AimTo evaluate the feasibility and efficacy of endovascular therapy in the initial segment of chronic vertebral basilar artery occlusion.Material and methodsThis is a retrospective study based on data obtained from Lishui Hospital of Zhejiang University. We identified patients who underwent treatment for initial segment occlusion of the vertebral basilar artery from September 2014 to September 2018.ResultsAmong a total of twenty-two subjects, 77.27% of them were men and the median age was 61 years old. The primary medical history of these patients included hypertension (15, 68.18%), hyperlipidemia (13, 59.09%), diabetes mellitus (11, 50.00%), and coronary artery disease (6, 27.27%). About 54.54% of the patients were current smokers. Successful recanalization was achieved in 86.36% of patients. Five cases of balloon dilatation were recanalized and fourteen cases were treated by balloon dilation combined with stent implantation. During the follow-up period, there were no recurrent cerebral ischemic events, including transient ischemic attack or stroke. Six (27.27%) arteries were found to exhibit angiographic re-stenosis.ConclusionsThe clinical effect of balloon dilatation or balloon dilatation combined with stenting in the treatment of chronic vertebral basilar artery occlusion in the beginning segment was feasible and safe.

Genotype-phenotype correlations and effect of mutation location in Japanese CADASIL patients.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary cerebral small vessel disease caused by NOTCH3, and characterized by recurrent cerebral ischemic events without vascular risk factors, mood disturbance, and dementia. MRI testing shows cerebral white matter hyperintensities, especially in the external capsule and temporal pole. Typical mutations are cysteine-related missense ones located in one of 34 EGF-like repeats (EGFr) in the NOTCH3 receptor. To identify genotype-phenotype correlations, 179 Japanese CADASIL probands were recruited. Of the 68 mutations identified, p.Cys388Arg, p.Cys435Phe, p.Gly481Cys, p.Cys743Tyr, and p.Cys1009Phe were novel ones. The genotype-phenotype correlation was analyzed based on the three most common mutations: p.Arg75Pro, p.Arg141Cys, and p.Arg182Cys. p.Arg141Cys showed typical CADASIL phenotypes, whereas p.Arg75Pro showed mild and atypical phenotypes, a low frequency of stroke/TIA, high frequency of hypertension, and low frequency of temporal pole lesions. p.Arg182Cys showed various initial symptoms other than stroke/TIA. Subsequently, we analyzed the effect of the mutation location on the age at onset of stroke/TIA. We found that mutations in EGFr 1-6 excluding the cysteine-sparing mutation p.Arg75Pro were significantly correlated with a younger age at onset of stroke/TIA compared with those in EGFr 7-34. This was in agreement with a recent European report, suggesting that the effect of the mutation location is a consensus finding in CADASIL worldwide.

Stroke : Highlights of Selected Articles

<i>Stroke</i> : Highlights of Selected Articles

Abstract WP72: Recurrent Cerebral Ischemic Events in Symptomatic Carotid Stenosis are Related to Plaque Inflammation

Background and Aims: Severity of symptomatic carotid stenosis often determines the treatment approach. However, severity explains only the regional hypoperfusion as the mechanism of cerebral ischemia. Artery-to-artery embolisation remains an important pathogenic mechanism in patients with high-risk carotid plaques. Inflammation is considered as the initiating event for plaque rupture and cerebral embolism. Using 18F-fluorodeoxyglucose positron-emission tomography (FDG-PET)/computed tomography (CT) and high-resolution magnetic resonance imaging (HR-MRI), we investigated the role of plaque imaging in stroke recurrence in our patients with recently symptomatic carotid stenosis. Methods: This prospective study included consecutive patients within 30-days of recent stroke and ipsilateral carotid stenosis (≥50%). FDG uptake was quantified as mean standardized uptake values (SUV, g/ml). The ratio of T1 hyperintensity of carotid plaque to the ipsilateral sternocleidomastoid muscle (SCM) was recorded on T1-weighted fat suppressed HR-MRI. Patients were followed-up for stroke recurrence within 90-days. Results: Of the 115 patients included in the study, 17 (15%) suffered from recurrent cerebral ischemic event in the stenosed carotid territory within 90-days. Compared to patients who remained asymptomatic, patients with recurrent cerebral ischemia showed higher mean T1 carotid-SCM ratio (2.19 versus 1.38; p&lt;0.0001) and higher mean SUV value in the carotid plaque (3.04g/ml versus 1.25g/ml; p&lt;0.0001). Higher T1 carotid-SCM ratio on HR-MRI (OR 3.215, 95%CI 1.304-5.927; p&lt;0.0001) and higher mean SUV on FDG-PET (OR 3.601, 95%CI 2.924-7.628; p=0.005) were independent predictors of recurrent cerebral ischemia. Conclusions: FDG-PET/CT and HR-MRI of carotid stenosis are useful tools for risk stratification and may aid in better therapeutic decision-making.

Long-term outcome in extracranial-intracranial bypass surgery for severe steno-occlusive disease of intracranial internal carotid or middle cerebral artery

ObjectivesWe report the long-term outcome and rates of recurrent cerebral ischemic events in our cohort of carefully selected patients after STA-MCA bypass for severe steno-occlusive disease of intracranial ICA or MCA with exhausted cerebral vasodilatory reserve. Patients and MethodsIn this retrospective study, we reviewed the hospital records for all patients who underwent direct superficial temporal artery-middle cerebral artery bypass surgery at our institution from January 2010 to August 2017. Patients were included in the study if they presented with transient ischemic attack or non-disabling stroke due to a severe steno-occlusive lesions of the intracranial internal carotid artery or middle cerebral artery with abnormal cerebral vasodilatory reserve on imaging. The overall event rate is defined as transient ischemic attack, acute ischemic stroke, peri-operative stroke or death. Results69 patients were included in the study. The median age of cohort was 57 years (inter-quartile range 36–78). Median follow up period in our study was 73 months (range 2–90 months). The overall event rate post-treatment during the follow up period is 20.2%. In contrast, previous studies have showed that patients who underwent best medical therapy had a higher recurrent ischemic stroke rate over a 2–3-year period. ConclusionThis study suggests that carefully selected patients with severe steno-occlusive disease and significantly abnormal cerebral hemodynamic reserve who undergo extracranial-intracranial bypass surgery, may benefit from long-term prevention of symptomatic cerebral ischemic events.

Abstract 147: Plaque Inflammation is Associated With Early Cerebral Ischemic Events in Symptomatic Carotid Stenosis

Background and aims: Currently, the severity of the symptomatic carotid stenosis determines the treatment approach. However, it explains only the regional hypoperfusion as the mechanism of cerebral ischemia. Artery-to-artery embolisation remains an important pathogenic mechanism in patients with high-risk carotid plaques. Recently, inflammation has been proposed as the initiating event for plaque rupture and cerebral embolism. Using 18F-fluorodeoxyglucose positron-emission tomography (FDG-PET)/computed tomography (CT) and high resolution magnetic resonance imaging (HR-MRI), we investigated the role of plaque imaging and stroke recurrence in our cohort of patients with recently symptomatic carotid stenosis. Methods: This ongoing prospective study included consecutive patients within 30-days of recent stroke and ipsilateral carotid stenosis (≥50%). FDG uptake was quantified as mean standardized uptake values (SUV, g/ml). The ratio of T1 hyperintensity of carotid plaque to the ipsilateral sternocleidomastoid muscle (SCM) was recorded on T1-weighted fat suppressed HR-MRI. Patients were followed prospectively for stroke recurrence within 90-days. Results: Of the 70 patients included in the study, 11 (16%) suffered from recurrent cerebral ischemic event in the same vascular territory within 90-days. Compared to patients without subsequent cerebral ischemic events, patients with recurrent cerebral ischemia showed higher mean T1 carotid-SCM ratio (2.24 versus 1.46; p&lt;0.0001) and higher mean SUV value in the carotid plaque (3.26g/ml versus 1.28g/ml; p&lt;0.0001). Higher T1 carotid-SCM ratio on HR-MRI (OR 3.374, 95%CI 1.561-6.253; p&lt;0.0001), higher mean SUV on FDG-PET (OR 3.646, 95%CI 3.172-11.524; p=0.005) were independent predictors of recurrent cerebral ischemia. Conclusions: FDG-PET/CT and HR-MRI of carotid stenosis helps in identification of patients at higher risk of subsequent cerebral ischemic events and may aid in better therapeutic decision-making.

Circulating miRNA levels differ with respect to carotid plaque characteristics and symptom occurrence in patients with carotid artery stenosis and provide information on future cardiovascular events.

IntroductionCirculating microRNAs (miRNAs) levels are potentially important biomarkers and therapeutic targets of cerebral ischemic event (CIE) in patients with internal carotid artery stenosis (ICAS).AimThis prospective study investigated associations between circulating miRNAs and symptomatic and asymptomatic ICAS, carotid plaque morphology and future cardiovascular events.Material and methodsCirculating miRNAs (miR-1-3p, miR-16-5p, miR-34a-5p, miR-124-3p, miR-133a-3p, miR-133b, miR-134-5p, miR-208b-3p, miR-375 and miR-499-5p) were analyzed in 92 consecutive patients with significant ICAS referred for revascularization. Group I comprised 65 subjects (41 males, age 69.3 ±9.7 years) with a recent CIE. Group II comprised 27 patients (15 males, age 68.2 ±8.4 years) with asymptomatic ICAS. The ICAS degree and plaque morphology was assessed by ultrasonography. The incidences of cardiovascular death (CVD), myocardial infarction (MI) and recurrent CIE (CVD/MI/CIE) were recorded prospectively (mean: 38.7 ±3.8 months).ResultsGroups II and I differed significantly in levels of miR-124-3p (p = 0.036), miR-133a-3p (p = 0.043) and miR-134-5p (p = 0.02). Hypoechogenic, as compared to echogenic, plaques differed in levels of miR-124-3p (p = 0.038), miR-34a-5p (p = 0.006), miR-133b (p = 0.048), miR-134-5p (p = 0.045), and miR-375 (p = 0.016), while calcified plaques differed in miR-16-5p (p = 0.023). Ulcerated plaques showed higher levels of miR-1-3p (p = 0.04) and miR-16-5p (p = 0.003), while thrombotic plaques showed lower levels of miR-1-3p (p = 0.032). CVD/MI/CIE occurred in 14 (15.5%) out of 90 follow-up patients. Multivariate Cox and ROC analysis showed associations between miR-1-3p and CVD (AUC = 0.634; HR = 4.84; 95% CI: 1.62–14.5; p = 0.005), MI (AUC = 0.743; HR = 7.8; 95% CI: 2.01–30.0; p = 0.003), and CVD/MI/CIE (AUC = 0.560; HR = 4.6; 95% CI: 1.61–13.1; p = 0.004), while miR-133b was associated with recurrent CIE (AUC = 0.581; HR = 2.25; 95% CI: 1.01–5.02; p = 0.047).ConclusionsA significant difference in levels of selected miRNAs is observed in symptomatic vs. asymptomatic ICAS. Plaque morphology and structure is associated with change of miRNA levels. The expression of miR-1-3p may be a potential prognostic factor for future cardiovascular events.