Risk Of Cerebral Ischemic Events Research Articles

The mid-term results of the Carotid Asymptomatic Stenosis (CARAS) observational study

IntroductionCarotid endarterectomy (CEA) in patients with asymptomatic carotid stenosis (ACAS) remains a subject of debate. Current recommendations are based on randomized trials conducted over 20 years ago and improvements in medical therapies may have reduced the risk of cerebral ischemic events (CIE). This study presents a mid-term analysis of results from an ongoing prospective observational study of ACAS patients to assess their CIE risk in a real-world setting. MethodsThis is a prospective observational cohort study of patients with ACAS >60 % (NASCET criteria) identified in a single duplex ultrasonography (DUS) vascular laboratory (trial registered: NCT04825080). Patients were not considered for CEA due to their short life expectancy (<3 year) or absence of signs of plaque vulnerability (ulceration, ipoechogenic core). Patient enrollment started in January 2019 and ended in March 2020 with a targeted sample size of 300 patients.A 5-year follow-up was scheduled. Clinical characteristics, risk factors, and medical therapies were documented, and, when necessary, the best medical therapy (BMT), involving antiplatelet agents, blood pressure control, and statins, was recommended during clinical visits. The primary endpoint was to asses CIEs (including strokes, transient ischemic attacks, amaurosis-fugax) ipsilateral to ACAS along with plaque progression rate and patients survival. Follow-up involved annual clinical visit and carotid DUS examination, complemented by telephone interviews at six-month intervals. ResultsThe study included 307 patients, with an average age of 80 ± 7 years, of whom 55 % were male. Contralateral stenosis exceeding 60 % was present in 61 (20 %) patients. Seventy-seven percent of patients were on BMT. At a mean follow-up of 41±9 months, 7 ispilateral strokes and 9 TIAs occurred, resulting in 14 CIEs (2 patients experienced both TIA and stroke). According to Kaplan–Meier analysis, the 4-year CIE rate was 6±2 %, with an annual CIE rate of 1.5 %. Fifty-eight (19 %) patients had a stenosis progression which was associated with a higher 4-year estimated CIE rate compared to patients with stable plaque (10.3 % vs 3.2 %, P=.01). Similarly, a contralateral carotid stenosis >60 % was associated with a higher 4-year estimated CIE rate: 11.7 % vs 2.9 %, P=.002. These factors were independently associated with high risk for CIE at the multivariate COX analysis: Hazard Ratio (HR): 3.2; 95 % Confidence Interval: 1.1-9.2 and HR: 3.6; 95 % CI: 1.2-10.5. ConclusionThe mid-term results of this prospective study suggest that the incidence of CIE in ACAS patients should not be underestimated, with plaque progression and contralateral stenosis serving as primary predictors of CIEs.

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.

Cerebral Ischemic Events Ipsilateral to Carotid Artery Stenosis. The Carotid Asymptomatic Stenosis (CARAS) Observational Study: First Year Preliminary Results

To report the characteristics of the prospective observational cohort study "Carotid Asymptomatic Stenosis (CARAS)", including patients with asymptomatic carotid stenosis under medical treatment and their first year of follow-up, in order to estimate the risk of cerebral ischemic events. This is a prospective observational cohort study of CARAS>60% (Nascet criteria) patients, identified in a single duplex-ultrasonography (DUS) vascular laboratory (trail registration N: NCT04825080). Patient's enrollment started in January 2019 and ended in March 2020 with the follow-up conclusion scheduled in December 2025. The aimed sample size was calculated at 300 patients for a 5-year follow-up. The primary outcome were the incidence of ipsilateral neurologic ischemic events (stokes and transient ischemic attacks [TIA]), plaque progression rate, and survival. The follow-up was scheduled at six-month intervals for clinical visit and annually for DUS examination. a total of 307 patients completed the first follow-up year. The mean age was 81±4 years, 55% were male. Contralateral stenosis >60% was present in 90 (29%) patients. Antiplatelet therapy and statins adherence was 80% and 88%, respectively. During the first year, 3 ispilateral strokes (1%) and 4 TIAs (1.3%) occurred, for a total of 2.3% ipsilateral ischemic events. During the first year, 43 (14%) plaques had a stenosis progression, which was correlated with the occurrence of neurological events (9.3% vs. 1.1%, P=.001, OR: 8.9; 95%CI: 1.9-41); 6 deaths (2%) occurred in the same period. the preliminary one-year results of this prospective study suggest that the overall rate of any ipsilateral ischemic event, and specifically ipsilateral strokes, correlates with plaque progression.

High Plasma Concentration of Apolipoprotein C-III Confers an Increased Risk of Cerebral Ischemic Events on Cardiovascular Patients Anticoagulated With Warfarin.

IntroductionApolipoprotein C-III (Apo CIII) is a crucial regulator of triglyceride-rich lipoproteins (TRLs) and influences the risk of cardiovascular diseases. High levels of Apo CIII have been also associated with cerebrovascular events and earlier works showed procoagulant effects of Apo CIII. The main aim was to assess whether the plasma concentration of Apo CIII could confer an increased risk of cerebral ischemic events in anticoagulated patients at high-risk of cardioembolism.MethodsWe systematically checked medical records and quantified cerebral ischemic events in a selected cohort of 118 subjects [median age 68 with interquartile range (IQR) 59–75 years, 66.9% males, 52.5% with coronary artery disease (CAD)], taking anticoagulant therapy with warfarin because of atrial fibrillation (AF) and/or mechanical prosthetic heart valves. All the subjects, enrolled between May 1999 and December 2006, were prospectively followed until death or July 31, 2018. Assessments of complete plasma lipid and apolipoprotein profiles, including Apo A-I, B, CIII, and E, were available for all subjects at enrollment.ResultsAfter a median follow-up of 109 months (IQR, 58–187), 24 subjects (20.3%) had cerebral ischemic events: stroke (n = 15) and TIA (n = 9). Subjects with plasma concentration of Apo CIII above the median value (10.3 mg/dL) had an about three-fold increased risk of stroke/TIA than those with lower levels of Apo C-III [hazard ratio 3.08 (95%CI, 1.22–7.77)]. This result was confirmed in multiple Cox regression models adjusted for gender, age, CAD, AF, diabetes, hypertension, plasma lipids, and CHA2DS2-VASc score. By stratifying the sample on the basis of Apo CIII level and CHA2DS2-VASc score, an additive effect was observed with the highest risk in subjects with both high Apo C-III concentration and CHA2DS2-VASc score.ConclusionHigh Apo CIII plasma levels may be associated with an increased risk of ischemic stroke/TIA in high-risk cardiovascular patients anticoagulated with warfarin.

Association between blood coagulability and migraine

BackgroundAn association between migraine and stroke has been suggested for a long period, although conclusive evidence has not been reported. Several theories about hypercoagulability have been proposed for the association of ischemic stroke and migraine especially migraine with aura. This study aimed to assess blood coagulability in patients with migraine.ResultsMean serum levels of protein S and anti-thrombin III were significantly lower in migraine patients compared to control subjects. Migraine patients showed abnormal MRI findings in the form of white matter hyper-intense lesions and ischemic foci compared to healthy controls. A significant negative correlation was detected between serum protein C level and intensity of migraine headache. Also, a significant correlation was found between deficient serum protein S and abnormal findings in brain MRI. Serum protein C deficiency is an independent predictor for migraine intensity grade.ConclusionsThere is an association between migraine and hypercoagulability, which may indicate increased risk of cerebral ischemic events in migraine patients and suggest adding prophylactic therapy to the management strategies of such patients.

Improvement of Cerebrovascular Reserve by Percutaneous Transluminal Angioplasty for Symptomatic Middle Cerebral Artery Stenosis.

The purpose of this study was to investigate the efficacy of percutaneous transluminal angioplasty (PTA) for symptomatic middle cerebral artery stenosis by analyzing cerebral blood flow (CBF). Between January 2016 and December 2018, six patients with symptomatic middle cerebral artery stenosis underwent CBF analysis by single-photon emission computed tomography (SPECT) with acetazolamide challenge before and after PTA for stenosis. They were retrospectively reviewed, and the blood flow in the area of the affected middle cerebral artery before and after angioplasty was compared. The mean stenosis rate and length of lesion before angioplasty were 76.4 ± 5.4% and 6.5 ± 2.1 mm, respectively. Balloon angioplasty without stenting was performed on all patients. The mean residual stenosis rate just after angioplasty was 45.4 ± 9.3%. No periprocedual complications developed, and there were no notable cerebral ischemic events during the postprocedural follow-up period. One patient underwent repeat angioplasty for restenosis. Although there was only a mild decrease in blood flow at rest, the cerebrovascular reserve (CVR) in the area of the affected middle cerebral artery was markedly decreased before angioplasty (mean, 3.6 ± 4.3%). After angioplasty, the CVR was significantly improved (mean, 18.0 ± 4.7%, p <0.01). PTA for symptomatic middle cerebral artery stenosis can be safely performed using appropriate interventional techniques for select patients. Reduced CVR due to stenosis can be improved after angioplasty, which may reduce the risk of cerebral ischemic events.

Atrial High-Rate Episodes and Their Association with Cerebral Ischemic Events in Chagasic Patients.

ResumoFundamentoEpisódios de alta frequência atrial (EAFAs) estão associados a um risco elevado de eventos isquêmicos cerebrais, porém não existem estudos relacionados com a presença de EAFAs e eventos isquêmicos cerebrais em pacientes chagásicos.ObjetivoInvestigar a associação entre a presença de EAFAs ≥ 6 minutos e eventos isquêmicos cerebrais em pacientes chagásicos.MétodosEstudo de coorte com pacientes chagásicos, portadores de dispositivos cardíacos eletrônicos implantáveis (DCEIs), acompanhados no ambulatório de arritmias de um hospital universitário, na cidade de Salvador/BA, entre maio de 2016 e junho de 2017. Pacientes com diagnóstico de flutter atrial/fibrilação atrial, com DCEI unicameral e em uso de anticoagulação oral foram excluídos. Foram considerados EAFAs com frequência atrial ≥ 190 batimentos por minuto e duração ≥ 6 minutos (min), e os eventos isquêmicos cerebrais foram identificados por meio de tomografia computadorizada (TC) de crânio.ResultadosOs 67 participantes da pesquisa (67,2% do sexo feminino, com idade média de 63,6 ± 9,2 anos) foram acompanhados por 98 ± 28,8 dias e 11,9% dos pacientes apresentaram EAFAs ≥ 6 minutos. A TC de crânio evidenciou eventos isquêmicos cerebrais silenciosos em 16,4% dos pacientes, sendo que, destes, 63,6% haviam apresentado os EAFAs ≥ 6 minutos na análise dos DCEIs. A idade avançada (OR 1,12 [IC 95% 1,03-1,21; p=0,009) e a presença de EAFAs ≥ 6 minutos (OR 96,2 [IC 95% 9,4-987,4; p<0,001]) foram preditores independentes para eventos isquêmicos.ConclusãoEAFAs detectados por DCEIs estavam associados à presença de eventos isquêmicos cerebrais silenciosos em pacientes chagásicos. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0)

Correlation between SHP-1 and carotid plaque vulnerability in humans

BackgroundAdvanced atherosclerotic plaques tend to indicate an increased risk of cerebral ischemic events. SH2 domain-containing protein tyrosine phosphatase 1 (SHP-1) is a class I classical nonreceptor protein tyrosine phosphatase associated with plaque stability, as shown by analysis of a Gene Expression Omnibus (GEO) dataset showing differences in mRNA levels. However, the correlation between SHP-1 and human carotid plaque stability at the protein level remains unclear. Methods and resultsThirty-nine carotid plaque tissue samples were acquired from 39 carotid artery stenosis patients after carotid endarterectomy. Hematoxylin and eosin, Masson trichrome, and CD68 staining was performed for pathological characterization, and immunohistochemical staining for SHP-1 was carried out. Within stable and unstable plaques, SHP-1 mainly accumulated in the necrotic area, plaque shoulder, and fibrous cap, similar to the distribution of CD68. A quantitative analysis of SHP-1 was carried out. The relative SHP-1-positive cell area was higher in the vulnerable group than in the stable group (P < .001). The number of symptomatic patients in the vulnerable group was no greater than that in the stable group (P = .098). Moreover, the integrated optical density (IOD)/area of SHP-1 was significantly higher in the vulnerable group than in the stable group (P < .001). Besides, SHP-1 colocalized with CD68 and vascular cell adhesion protein 1(VCAM-1). ConclusionsWe demonstrate that SHP-1 expression increases during carotid atherosclerotic plaque progression. The protein expression of SHP-1 was related to an increase in plaque instability in not only symptomatic but also asymptomatic patients with carotid artery stenosis. SHP-1 may play a role in atherosclerosis progression by macrophage polarization-mediated efferocytosis. Furthermore, SHP-1 may become a promising biomarker for plaque vulnerability in the future.

Dynamic change of carotid intraplaque hemorrhage volume in subjects with mild carotid stenosis

Background and PurposeEarly detection of intraplaque hemorrhage (IPH) in the carotid artery is important as it is correlated with an increased risk of cerebral ischemic events. We examined changes in IPH with magnetic resonance imaging (MRI) over an extended follow-up period in patients with mild carotid stenosis. Materials and MethodsFrom November 2013 to November 2015, we retrospectively reviewed cerebral MRI of 2036 patients, including magnetization-prepared rapid acquisition with gradient-echo (MPRAGE) sequences obtained with a 3.0 T (T) MRI unit. An experienced neuroradiologist reviewed all studies and found 38 patients with carotid IPH and carotid stenosis that were categorized as mild (<30%), according to the North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria. Twenty-five patients agreed to join this study and signed informed consent for (MPRAGE) sequence imaging. We used semi-automated software to measure IPH volume on both the initial and follow up scans. ResultsThe median follow-up time of patients with mild carotid stenosis and IPH was 33.3 months. IPH volume increased in 10 of 27 carotid arteries (37.0%), with a mean volume increase of 42.6 ± 44.0 mm3. IPH volume decreased in 17 of 27 carotid arteries (63%), with a mean volume decrease of 17.2 ± 22.8 mm3. Two patients without IPH at baseline showed IPH development on follow-up imaging. There were no significant differences in patient demographics between the two groups. ConclusionsCarotid IPH volume in subjects with mild carotid stenosis can change over time and may not be correlated with any typical patient demographics.

Long-Term Population-Based Cerebral Ischemic Event and Cognitive Outcomes of Direct Oral Anticoagulants Compared With Warfarin Among Long-term Anticoagulated Patients for Atrial Fibrillation

Direct oral anticoagulants (DOACs) have been used in clinical practice in the United States for the last 4 to 6years. Although DOACs may be an attractive alternative to warfarin in many patients, long-term outcomes of use of these medications are unknown. We performed a propensity-matched analysis to report patient important outcomes of death, stroke/transient ischemic attack (TIA), bleeding, major bleeding, and dementia in patients taking a DOAC or warfarin. Patients receiving long-term anticoagulation from June 2010 to December 2014 for thromboembolism prevention with either warfarin or a DOAC were matched 1:1 by index date and propensity score. Multivariable Cox hazard regression was performed to determine the risk of death, stroke/TIA, major bleed, and dementia by the anticoagulant therapy received. A total of 5,254 patients were studied (2,627 per group). Average age was 72.4 ± 10.9 years, and 59.0% were men. Most patients were receiving long-term anticoagulation for AF management (warfarin: 96.5% vs DOAC: 92.7%, p <0.0001). Rivaroxaban (55.3%) was the most commonly used DOAC, followed by apixaban (22.5%) and dabigatran (22.2%). The use of DOACs compared with warfarin was associated with a reduced risk of long-term adverse outcomes: death (p= 0.09), stroke/TIA (p <0.0001), major bleed (p <0.0001), and bleed (p= 0.14). No significant outcome variance was noted in DOAC-type comparison. In the AF multivariable model patients taking DOAC were 43% less likely to develop stroke/TIA/dementia (hazard ratio 0.57 [CI 0.17, 1.97], p= 0.38) than those taking warfarin. Our community-based results suggest better long-term efficacy and safety of DOACs compared with warfarin. DOAC use was associated with a lower risk of cerebral ischemic events and new-onset dementia.

Aortic Complex Plaque Predicts the Risk of Cryptogenic Ischemic Cerebrovascular Disease Recurrence.

To evaluate the correlations between aortic complex plaque (ACP) and the recurrence of cryptogenic ischemic cerebrovascular disease (CICVD), and to investigate the clinical significance of ACP in CICVD. Methods CICVD patients (aged 17 to 84 years) admitted into the Department of Neurology, Xuanwu Hospital, from July 2011 to December 2013, were consecutively recruited, and divided into ACP and non-ACP groups according to head and neck computerized tomographic (CT) angiography. Recurrences of cerebral ischemic events (CIEs) were compared between these groups after follow-up. Results A total of 117 patients were enrolled (ACP group: 69, non-ACP group: 48) and followed up for a mean of 9.86 months (range: 3-33). The average age of the ACP group was 62.88 years, with 59.4% older than 60 years; the average age of the non-ACP group was 50.29 years, with 37.5% older than 60 years. At the 6-month follow-up, the recurrence rate of CIEs in the ACP group was significantly higher than that of the non-ACP group (17.0% [7/47] and 0% [0/36], respectively; χ2 = 4.283, P = 0.046). The cumulative recurrence risk for CIEs of the ACP group was significantly higher than for the non-ACP group (P = 0.004). Multivariate Cox survival analysis showed that ACP presence was an independent risk factor for CIE recurrence for CICVD patients (relative risk [RR] = 7.803, 95% confidence interval [CI], 1.827~33.319, P = 0.006). Conclusions ACP increased the recurrence risk of CIE in CICVD, and elderly CICVD patients should receive greater attention regarding the significance of ACP in recurrent CICVD.

Abstract 173: Current Treatment Status and Predictors of Subsequent Cerebral Ischemic Events in Transient Ischemic Attack Patients with Symptomatic Carotid Stenosis

Background and Purpose: Patients with symptomatic carotid stenosis (SCS) have recently tended to receive aggressive treatments including dual antiplatelet (AP) therapy and early carotid revascularization. The aim of this study was to clarify the current treatment status and predictors of subsequent cerebral ischemic events in TIA patients with SCS. Methods: The PROMISE TIA registry prospectively enrolled 1,353 patients with TIA within 7 days of onset from 57 hospitals in Japan between June 2011 and December 2013. All SCS patients were extracted from this registry and divided into 3 stenosis groups; mild (&lt;50%), moderate (50-69%) and severe (≥70%). The endpoint events were ischemic stroke/recurrent TIA within 90 days of index TIA. Results: A total of 125 patients (103 men, 73.5±8.8 years old) was included. Thirty-seven patients (29.6%) had mild, 45 (36.0%) had moderate, and 43 (34.4%) had severe SCS. The rates of men and patients with amaurosis fugax (AF) were higher with increasing severity of SCS (men, 70.3% vs 80.0% vs 95.3%, p=0.012; AF, 0% vs 4.4% vs 16.3%, p=0.013). Acute-phase treatments using multiple AP with or without anticoagulant (AC) therapy were performed in 61 patients (48.8%), and 47 patients (37.6%) underwent revascularization within 90 days. The rates of patients receiving multiple AP with AC and those undergoing revascularization were higher with increasing severity of SCS (multiple AP with AC, 8.1% vs 37.8% vs 41.9%, p&lt;0.001; revascularization, 10.8% vs 31.1% vs 67.4%, p&lt;0.001). The endpoint events occurred in 9 patients (7.6%); 2 (5.7%) in mild group, 6 (14.0%) in moderate group and 1 (2.4%) in severe group (p=0.121). On multivariate analysis, dual TIA (HR, 5.9; 95%CI, 1.3-28) predicted the endpoint events. Conclusion: In TIA patients with SCS, the rates of treatments with multiple AP and revascularization procedures were approximately 50% and 40%, respectively, being increasingly frequent with increasing severity of SCS. The 90-day risk of cerebral ischemic events was 7.6%, and patients with SCS who experienced dual TIA might need the aggressive treatments, regardless of severity of SCS.

Abstract T P137: Cerebral Ischemic Events In Patients With Therapeutic Warfarin Treatment

Background: Patients on long term warfarin treatment can have cerebral ischemic events despite therapeutic levels. We sought to determine unique patient attributes that result in ischemic events on therapeutic warfarin treatment. Methods: We reviewed the medical records and imaging data of consecutive patients with cerebral ischemic events who were on long term warfarin treatment over a 4 year period. We stratified the patients based on international normalized ratio (2.0-3.0 versus &lt;2.0) and compared the demographic and clinical characteristics between the two groups of patients. Results: A total of 163 patients (mean age±SD; 77.3 ± 11.2) on long term warfarin treatment were admitted with cerebral ischemic events (97 ischemic strokes and 40 transient ischemic attacks). The mean age was not different between patients who were sub therapeutic and therapeutic on warfarin (78.2 ±11.6 versus 77.5±10.5, p=0.7). The proportion of patients with hypertension (87.2% versus 84.0%, p=0.6), diabetes mellitus (44.2% versus 50.0 %, p=0.5), and cigarette smoking (7.0% versus 6.0%, p=0.8), was similar between the two groups. Patients who were therapeutic on warfarin were more likely to have large vessel atherosclerosis (8.0% versus 2.3 %, p=0.1) and small vessel disease (2.0% versus 1.2 %, p=0.6) and less likely to have atrial fibrillation (66.0% versus 77.5%, p=0.2) as the underlying etiologies for ischemic events. IV alteplase was used in 5 and none of patients who were sub therapeutic and therapeutic on warfarin, respectively. Conclusions: Patients who have concurrent predisposing factors appear to be at risk for cerebral ischemic events despite therapeutic warfarin treatment and concomitant preventive strategies should be evaluated.

Cerebrovascular reactivity by quantitative magnetic resonance angiography with a co2 challenge. Validation as a new imaging biomarker

Assessment of cerebrovascular reactivity (CVR) is essential in cerebrovascular diseases, as exhausted CVR may enhance the risk of cerebral ischemic events. Transcranial Doppler (TCD) with a vasodilatory stimulus is currently used for CVR evaluation. Scanty data are available for Quantitative Magnetic Resonance Angiography (QMRA), which supplies higher spatial resolution and quantitative cerebral blood flow values. Aims of our pilot study were: (a) to assess safety and feasibility of CO2 administration during QMRA, (b) evaluation of CVR under QMRA compared to TCD, and (c) quantitative evaluation of blood flow from the major intracranial arterial vessels both at rest and after CO2.CVR during 5% CO2 air breathing was measured with TCD as a reference method and compared with QMRA.Fifteen healthy subjects (age 60.47±2.24; male 11/15) were evaluated at rest and during CO2 challenge. Feasibility and safety of QMRA under CO2 were ensured in all subjects. CVR from middle cerebral artery territory was not statistically different between TCD and MRI (p>0.05). Mean arterial pressure (MAP) and heart rate (HR) increased during QMRA and TCD (MAP p=0.007 and p=0.001; HR p=0.043 and p=0.068, respectively). Blood flow values from all intracranial vessels increased after CO2 inhalation (p<0.001).CO2 administration during QMRA sessions is safe and feasible. Good correlation in terms of CVR was obtained comparing TCD and QMRA. Blood flow values significantly increased from all intracranial arterial vessels after CO2. Studies regarding CVR in physiopathological conditions might consider the utilization of QMRA both in routine clinical settings and in research projects.

Abstract T MP29: Impaired Vasodilatory Reserve on Acetazolamide-Challenged 99tc-hmpao-Spect is a Strong Predictor of Stroke Recurrence in Patients With Severe Steno-Occlusive Disease of Intracranial Carotid or Middle Cerebral Artery

Background: Intracranial stenosis carries an increased risk for cerebrovascular ischemia. In severe stenosis, cerebral autoregulation may be impaired due to inadequate cerebral vasodilatory reserve (CVR) &amp; intracranial steal phenomenon (reversed-Robin Hood syndrome-RRHS). Identification of patients with inadequate CVR and RRHS may help in identifying high-risk patients. Methods: In this prospective study, we included patients with symptomatic and severe stenosis of intracranial carotid (ICA) &amp; middle cerebral artery (MCA). CVR was evaluated with transcranial Doppler (TCD) and breath-holding index (BHI) &lt;0.69 determined inadequate CVR. RRHS was detected as transient velocity reduction in affected artery when flow increased in the reference artery. Patients with RRHS were further evaluated with acetazolamide-challenged 99Tc-HMPAO-SPECT. Results: 126 patients (80 male, mean age 56yrs; range 23-78yrs) fulfilled our TCD criteria for inadequate CVR. HMPAO-SPECT showed impaired CVR in 84 (67%) patients. RRHS noted on TCD in 38 (45%) patients (median steal magnitude 14%; inter-quartile range, IQR 10) was confirmed by acetazolamide-challenged HMPAO-SPECT (median perfusion deficit 8%; IQR 13%) in 35 (92%) cases (sensitivity 82%, specificity 96% with positive predictive value 96%). A strong relationship between RRHS on TCD and SPECT was noted on ROC curve analysis (area under curve 0.93; 95% confidence interval 0.87-0.98;p&lt;0.00001). Linear relationship was observed between impaired vasodilatory reserve and stroke recurrence during follow up (mean 35months; range 8 to 49months)- 56% in patients with RRHS versus 20% in patients with moderately impaired CVR versus 4% in patients with mildly impaired CVR (chi-square 18.42; df=2; p&lt;0.001 for trend). RRHS on HMPAO-SPECT was an independent predictor of recurrent cerebral ischemic events (RR 1.9, 95%CI 1.2-4.2; p=0.03). Conclusions: Among patients with severe intracranial stenosis, intracranial steal phenomenon is associated with high risk of cerebral ischemic events. Acetazolamide-challenged HMPAO-SPECT is reliable in the quantification of vasodilatory reserve for selecting a target group of patients for possible revascularization.

Abstract TP150: Intracranial steal phenomenon in Patients with Severe Steno-occlusive Disease of Intracranial Carotid or Middle Cerebral Artery

Background: Intracranial stenosis is a strong risk factor for stroke recurrence. In severe stenosis, perfusion is maintained by collaterals and cerebral autoregulation (CA). CA may be impaired due to inadequate cerebral vasodilatory reserve (CVR) &amp; intracranial steal phenomenon, so called ‘reversed-Robin Hood syndrome (RRHS)’. Identification of patients with inadequate CVR and RRHS may help in selecting high-risk patients. Methods: We prospectively included patients with symptomatic and severe stenosis of intracranial carotid (ICA) &amp; middle cerebral artery (MCA). CVR was evaluated with TCD &amp; breath-holding index (BHI) &lt;0.69 represented inadequate CVR. RRHS was detected as transient velocity reduction in affected artery when flow increased in the reference artery. Patients with RRH were further evaluated with acetazolamide-challenged HMPAO-SPECT. Results: TCD detected inadequate CVR in 112 patients (79 males, mean age 57yrs; range 23-79yrs) with severe intracranial stenosis of ICA or MCA. RRHS with a median steal magnitude of 17% (inter-quartile range, IQR 10) was seen in 35 (31%) patients. HMPAO-SPECT demonstrated perfusion deficit (median 8%; IQR 13%) in 33 out of these 35 cases (sensitivity 78%, specificity 96% with positive predictive value 96%). A strong relationship between RRH on TCD and SPECT was noted on ROC curve analysis (area under curve 0.93; 95% confidence interval 0.88-0.98;p&lt;0.00001). Linear relationship was seen between TCD steal magnitude and SPECT (Pearson correlation coefficient, r=0.643;p&lt;0.0001). Patients with RRHS were at a higher risk of developing recurrent cerebral ischemia (RR 1.7, 95%CI 1.2-3.6; p=0.04). Conclusions: Intracranial steal phenomenon in patients with severe intracranial stenosis is associated with high risk of cerebral ischemic events. Acetazolamide-challenged HMPAO-SPECT is reliable in the diagnosis of reversed Robin Hood syndrome in patients with severe steno-occlusive disease of intracranial carotid and middle cerebral artery. Identification of RRHS might help in identifying a target group of patients for possible revascularization

Incidence of cerebral ischemic events after discontinuation of clopidogrel in patients with intracranial aneurysms treated with stent-assisted techniques

The optimal antiplatelet medication protocol for prevention of thrombotic complications after stent-assisted coil embolization of cerebral aneurysms is unclear. Early cessation of antiplatelet agents may be associated with an increased risk of cerebral ischemic events. In this study, the authors assess the incidence of stroke or transient ischemic attack (TIA) following discontinuation of a 6-week course of clopidogrel in patients with cerebral aneurysms treated with stent-assisted techniques. A retrospective review was conducted in all patients with cerebral aneurysms undergoing stent-assisted coil embolization or stent-in-stent flow diversion at the University of Iowa during a 24-month period. The antiplatelet protocol was 81 mg aspirin and 75 mg clopidogrel daily for 6 weeks, followed by 325 mg aspirin daily indefinitely. The incidence of stroke or TIA was determined by a retrospective review of medical records generated during a 3-month period following discontinuation of clopidogrel. A total of 154 patients underwent aneurysm treatment with stent techniques during this interval. Documentation of neurological follow-up 3 months after discontinuation of a 6-week clopidogrel treatment was available in 121 (78.6%) of 154 patients. Of these 121 patients, 114 were treated with stent-assisted coil embolization and 7 with stent-in-stent flow diversion. Six patients (5%) suffered an ischemic event after cessation of clopidogrel, with 2 events occurring within the first 2 weeks. Specifically, the rate of ischemic events was 5 (4.3%) of 114 in the "stent-coil" treatment group and 1 (14.3%) of 7 in the stent-in-stent group. Treatment had been performed in the setting of a subarachnoid hemorrhage in 1 patient. Atypical aneurysm features and technical factors predisposing to thrombotic events were found in all but one of these patients. Similarly, cardiovascular risk factors were present in 5 of the 6 patients in whom ischemic events developed after clopidogrel discontinuation. Clopidogrel discontinuation is associated with a 5% risk of ischemic events in patients treated with stent techniques. Any stroke related to clopidogrel discontinuation is avoidable, and longer treatment is therefore clearly necessary. Patients with cardiovascular risk factors, high-risk aneurysm features, and those undergoing stent-in-stent flow diversion might benefit the most from longer clopidogrel therapy.

High Serum Total Cholesterol Levels as a Risk Factor of Ischemic Stroke in Asian Individuals

Evaluation of: Cui R, Iso H, Yamagishi K et al.; JPHC Study Group. High serum total cholesterol levels is a risk factor of ischemic stroke for general Japanese population: the JPHC study. Atherosclerosis 221(2), 565–569 (2012). An elevated cholesterol level is one of the established modifiable risk factors for secondary prevention of stroke. However, the stroke–cholesterol relationship remains a relatively weak relationship. Furthermore, the controversy regarding the optimal cholesterol level still persists. While elevated cholesterol levels are associated with higher risk for cerebral ischemic events, lower levels might increase the risk for hemorrhagic events. This study by Cui and colleagues presents robust large-scale epidemiological data regarding the association of elevated total cholesterol with the stroke risk among the Asian cohort. One of the important findings of this study is the relationship between elevated cholesterol and large artery atherosclerotic stroke. This is especially relevant in the Asian context, where large artery atherosclerosis constitutes more than half of all ischemic stroke subtypes. This paper reviews the study by Cui and colleagues regarding the role of high serum total cholesterol as a risk factor for ischemic stroke in Japanese men.

Metabolic Rehabilitation

See related article, page 3347. Type 2 diabetes is a well-recognized risk factor for cerebrovascular disease. In this issue of Stroke , Thacker et al1 demonstrate that earlier abnormalities in carbohydrate metabolism, insulin resistance, and impaired glucose tolerance are also associated with increased risk for cerebral ischemic events. These findings are reliable and timely, and they have immediate implications for the design of the next generation of stroke prevention trials. Abnormal carbohydrate metabolism comprises a spectrum of disorders characterized by impaired energy utilization. Early manifestations include obesity, decreased insulin sensitivity, impaired fasting glucose, and impaired glucose tolerance. The latter 2 conditions are often referred to as “prediabetes,” a stark description of their typically progressive nature. The most advanced manifestation, type 2 diabetes, results from the inexorable loss of insulin secretory capacity in the face of well-established insulin resistance. These metabolic states have become endemic in most countries as westernized lifestyles are adopted. In the United States alone, there are now 26 million individuals with diabetes and 79 million with prediabetes. Globally, the number of diabetic patients is now estimated to be 366 million. Clinicians who care for stroke patients know that metabolic disease is also prevalent in this population. Among patients with ischemic cerebrovascular disease, 18% to 30% are obese, 25% to 30% are insulin-resistant, 23% to 28% have impaired glucose tolerance, and 13% to 36% have diabetes.2–5 The Figure illustrates a model of impaired glucose regulation and its potential causal relationship to stroke. Each of its cardinal manifestations (ie, obesity, insulin resistance, hyperglycemia, diabetes) have been associated with increased risk for stroke.6 However, the evidence is strongest for obesity and diabetes, possibly because these are easiest to measure and classify. Obesity (body mass index ≥30 kg/m2) doubles the risk for ischemic stroke, …

Association Between Carotid Atherosclerosis Plaque With High Signal Intensity on T1-Weighted Imaging and Subsequent Ipsilateral Ischemic Events

An association between magnetic resonance imaging detection of intraplaque hemorrhage and the risk of cerebral ischemic events has been described. However, few studies have followed patients with intraplaque hemorrhage. We used 3-dimensional gradient-echo black-blood T1-weighted imaging (screening BB [S-BB]) as a magnetic resonance imaging sequence to evaluate acute cerebrovascular stroke. The association between S-BB high signal plaques and the risk of subsequent ipsilateral ischemic events was investigated. A total of 928 consecutive patients hospitalized for a stroke or transient ischemic attack according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification were evaluated. Recurrence was retrospectively evaluated in S-BB-positive patients and patients with severe stenosis (SS) (≥70%) by magnetic resonance angiography. Based on clinical and imaging findings, recurrence was defined as a carotid artery stroke or transient ischemic attack that developed after hospital discharge as an initial event. Sixty-six patients were S-BB positive and 62 patients had severe stenosis (S-BB positive with SS, 32 patients; S-BB negative with SS, 30 patients; S-BB positive without SS, 34 patients). During a mean follow-up period of 9.1 months, 7 S-BB-positive patients with SS (18.7%) and 1 S-BB-negative patient with SS (3%) had a recurrent event (P = .051). In the S-BB-positive group, in 34 patients without SS, the recurrence rate was 14.7% (5/34); the difference in the recurrence rate between S-BB-positive group with and without SS was not significant (P = .34). Patients with carotid artery lesions and intraplaque hemorrhage tend to be at higher risk of a subsequent ipsilateral ischemic event. Risk evaluation of carotid artery disease should include plaque characteristics.