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This case raises the potential association between cervical arterial dissection and VZV vasculopathy. We advise angiographic imaging of neck vessels when VZV vasculopathy is suspected.

Background and Purpose— Plaque inflammation contributes to stroke and coronary events. 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) identifies plaque inflammation-related metabolism. Almost no prospective data exist on the relationship of carotid 18 F-FDG uptake and early recurrent stroke. Methods— We did a multicenter prospective cohort study BIOVASC (Biomarkers/Imaging Vulnerable Atherosclerosis in Symptomatic Carotid disease) of patients with carotid stenosis and recent stroke/transient ischemic attack with 90-day follow-up. On coregistered carotid 18 F-FDG PET/computed tomography angiography, 18 F-FDG uptake was expressed as maximum standardized uptake value (SUV max ) in the axial single hottest slice. We then conducted a systematic review of similar studies and pooled unpublished individual-patient data with 2 highly similar independent studies (Dublin and Barcelona). We analyzed the association of SUV max with all recurrent nonprocedural stroke (before and after PET) and with recurrent stroke after PET only. Results— In BIOVASC (n=109, 14 recurrent strokes), after adjustment (for age, sex, stenosis severity, antiplatelets, statins, diabetes mellitus, hypertension, and smoking), the hazard ratio for recurrent stroke per 1 g/mL SUV max was 2.2 (CI, 1.1–4.5; P =0.025). Findings were consistent in the independent Dublin (n=52, hazard ratio, 2.2; CI, 1.1–4.3) and Barcelona studies (n=35, hazard ratio, 2.8; CI, 0.98–5.5). In the pooled cohort (n=196), 37 recurrent strokes occurred (29 before and 8 after PET). Plaque SUV max was higher in patients with all recurrence ( P P =0.009). The fully adjusted hazard ratio of any recurrent stroke was 2.19 (CI, 1.41–3.39; P P =0.008). Recurrent stroke risk increased across SUV max quartiles (log-rank P =0.003). The area under receiver operating curve for all recurrence was 0.70 (CI, 0.59–0.78) and for post-PET recurrence was 0.80 (CI, 0.64–0.96). Conclusions— Plaque inflammation-related 18 F-FDG uptake independently predicted future recurrent stroke post-PET. Although further studies are needed, 18 F-FDG PET may improve patient selection for carotid revascularization and suggest that anti-inflammatory agents may have benefit for poststroke vascular prevention.

To investigate the association between periventricular white mater hyperintensities (PVWMH) and biomarkers of elevated cerebral β-amyloid (Aβ) in the Alzheimer's Disease Neuroimaging Initiative, a large prospective multicenter observational study.The burden of frontal, parietal, and occipital PVWMH on 3T fluid-attenuated inversion recovery MRI was evaluated in 698 cognitively normal participants and participants with mild cognitive impairment (MCI) using a novel semiquantitative visual rating scale. Results were correlated with CSF-Aβ, florbetapir-PET, and fluorodeoxyglucose (FDG)-PET.Increased burden of parietal, occipital, and frontal PVWMH was associated with elevated cerebral amyloid evidenced by high florbetapir-PET signal (p0.01) and low CSF-Aβ (p0.01). In logistic regression models, including PVWMH, age, sex, APOE status, vascular risk factors, pulse pressure, vascular secondary prevention medications, education, ethnicity, and race, parietal, occipital, and frontal PVWMH burden was independently associated with high florbetapir-PET uptake (p0.05). In a similar logistic regression model, parietal and occipital (p0.05) but not frontal (p = 0.05) PVWMH were independently associated with CSF-Aβ. Weaker associations were found between parieto-occipital PVWMH and elevated CSF-tau (p0.05) and occipital PVWMH and elevated CSF-phospho-tau (p0.05). PVWMH were associated with cerebral hypometabolism on FDG-PET independent of CSF-Aβ levels (p0.05). Absolute and consistency of agreement intraclass correlation coefficients were, respectively, 0.83 and 0.83 for frontal, 0.78 and 0.8 for parietal, and 0.45 and 0.75 for occipital PVWMH measurements.Increased PVWMH were associated with elevated cerebral amyloid independent of potential confounders such as age, APOE genotype, and vascular risk factors. The mechanisms underlying the association between PVWMH and cerebral amyloid remain to be clarified.

Background and Purpose— Few recent studies have investigated the rates and predictors of early and late stroke recurrence using prospective population–based methodology. We investigated recurrent stroke at 2 years in the North Dublin Population Stroke Study (NDPSS). Methods— Patients were ascertained from December 2005 to 2006 from overlapping community and hospital sources using hot and cold pursuit. Stroke recurrence, survival, and functional outcome were ascertained at 72 hours, 7 days, 28 days, 90 days, 1 year, and 2 years. Results— Of 567 patients, cumulative 2-year stroke recurrence rate was 10.8% and case fatality was 38.6%. Recurrence subtype was associated with initial stroke subtype ( P P =0.005) and prior stroke (adjusted hazard ratio, 2.92; P =0.01) were independent predictors of 2-year recurrence in 28-day survivors. Conclusions— Despite rigorous ascertainment, recurrent stroke rates were lower in current study than in earlier studies. Our data suggest that large sample sizes may be needed for future secondary prevention trials in patients treated with modern preventive medications.

Objective: We hypothesized that serum lipids, which experimental data suggest may be key initiators of carotid plaque inflammation, would be associated with plaque inflammation on 18 fluorodeoxyglucose (FDG)-PET in patients with acutely symptomatic carotid stenosis. Methods: In this cohort study, consecutive patients with acute symptomatic internal carotid artery (ICA) stenosis (≥50%) underwent carotid PET-CT. We quantified plaque FDG uptake as follows: (1) average maximum standardized uptake values (SUV max ) across 10 regions of interest (ROI); (2) highest single ROI SUV measure (SUV ROImax ); (3) averaged mean SUV across 10 ROIs (SUV mean ). Results: Sixty-one patients were included. Plaque inflammatory FDG SUV max was associated with increasing tertiles of low-density lipoprotein (LDL) (trend p = 0.004), total cholesterol ( p = 0.009), and triglycerides ( p = 0.01), and with lower high-density lipoprotein (HDL) ( p = 0.005). When analyzed as a continuous variable, LDL was associated with symptomatic ICA SUV mean (Spearman rho 0.44, p = 0.009), SUV ROImax (rho 0.33, p = 0.01), and SUV max (rho 0.35, p = 0.06). Total cholesterol was associated with SUV mean (rho 0.33, p = 0.009), with trends for SUV max (rho 0.24, p = 0.059) and SUV ROImax (rho 0.23, p = 0.08). Triglycerides were associated with SUV max (rho 0.32, p = 0.01) and SUV ROImax (rho 0.35, p = 0.005). HDL was associated with lower SUV max (rho −0.37, p = 0.004) and SUV ROImax (rho −0.44, p = 0.0004). On multivariable linear regression analysis adjusting for age, sex, degree of carotid stenosis, statins, and smoking, LDL ( p = 0.008) and total cholesterol ( p = 0.04) were independently associated with SUV max . Conclusion: Serum LDL and total cholesterol were associated with acutely symptomatic carotid plaque FDG uptake, supporting experimental data suggesting lipids may promote plaque inflammation, mediating rupture and clinical events.

Background and Purpose— The World Health Organization has emphasized the importance of international population-based data for unbiased surveillance of stroke incidence and outcome. To date, few such studies have been conducted using recommended gold-standard ascertainment methods. We conducted a large, population-based stroke study in Dublin, Ireland. Methods— Using gold-standard ascertainment methods, individuals with stroke and transient ischemic attack occurring over a 12-month period (December 1, 2005–November 30, 2006) in North Dublin were identified. Disability was assessed using the modified Rankin score and stroke severity ( Results— Seven hundred one patients with new stroke or transient ischemic attack were ascertained (485 first-ever stroke patients, 83 recurrent stroke patients, 133 first-ever transient ischemic attack patients). Crude frequency rates (all rates per 1000 person-years) were: 1.65 (95% CI, 1.5–1.79; first-ever stroke), 0.28 (95% CI, 0.22–0.35; recurrent stroke), and 0.45 (95% CI, 0.37–0.53; first-ever transient ischemic attack). Age-adjusted stroke rates were higher than those in 9 other recent population-based samples from high-income countries. High rates of subtype-specific risk factors were observed (atrial fibrillation, 31.3% and smoking, 29.1% in ischemic stroke; warfarin use, 21.2% in primary intracerebral hemorrhage; smoking, 53.9% in subarachnoid hemorrhage; P Conclusions— Using gold-standard methods for case ascertainment, we found high incidence rates of stroke in Dublin compared with those in similar high-income countries; this is likely explained in part by high rates of subtype-specific risk factors.

Background and Purpose— Although therapeutic anticoagulation improves early (within 1 month) outcomes after ischemic stroke in hospital-admitted patients with atrial fibrillation, no information exists on late outcomes in unselected population-based studies, including patients with all stroke (ischemic and hemorrhagic). Methods— We identified patients with atrial fibrillation and stroke in a prospective, population-based study in North Dublin. Clinical characteristics, stroke subtype, stroke severity (National Institutes of Health Stroke Scale), prestroke antithrombotic medication, and International Normalized Ratio (INR) at onset were documented. Modified Rankin Scale (mRS) score was measured before stroke and at 7, 28, and 90 days; 1 year; and 2 years after stroke. Results— One hundred seventy-five patients had atrial fibrillation–associated stroke and medication data at stroke onset (159 ischemic, 16 hemorrhagic); 17% of those with ischemic stroke were anticoagulated before stroke (27 of 159.) On multivariable analysis, therapeutic INR was associated with improved late survival after ischemic stroke (adjusted 2-year odds ratio for death=0.08; 95% CI, 0.01 to 0.78; P =0.03). This survival benefit persisted when patients with hemorrhagic stroke were included (2-year survival; 70.5% therapeutic INR, 14.3% nontherapeutic INR; log-rank P P =0.03). Admission INR was inversely correlated with early and late modified Rankin Scale score (2-year Spearman ρ=−0.65; P P =0.04) and good functional outcome (modified Rankin Scale score=0 to 2) at 1 year (adjusted odds ratio=4.8; 95% CI, 1.45 to 23.8; P =0.04). Conclusions— In addition to improving short-term outcome in selected hospital-treated patient groups, therapeutic anticoagulation may provide important benefits for long-term stroke outcomes in unselected populations.

Objective: In the North Dublin Population Stroke Study, we investigated the risk of recurrent stroke within the 14-day time window recommended for endarterectomy. Methods: In a population-based prospective cohort study, all ischemic stroke patients were identified over 1 year and categorized into those with (CS-positive) and without (CS-negative) ipsilateral carotid stenosis (CS) (≥50% lumen narrowing). Nonprocedural stroke recurrence was determined at 72 hours and 7 and 14 days. Results: Of 365 ischemic stroke patients with carotid imaging, 51 were excluded due to posterior circulation or nonlateralizing stroke, ipsilateral carotid occlusion, or intracranial stenosis, leaving 314 included for analysis (36 CS-positive and 278 CS-negative). Recurrent stroke occurred in 5.6% (2/36) CS-positive and 0.4% (1/278) CS-negative patients by 72 hours of symptom onset ( p = 0.003), 5.6% (2/36) CS-positive and 0.7% (2/278) CS-negative patients ( p = 0.01) by 7 days, and in 8.3% (3/36) CS-positive and 1.8% (5/278) CS-negative patients by 14 days ( p = 0.02). On multivariable Cox regression analysis, CS was the only independent predictor of recurrence at 72 hours (adjusted hazard ratio [HR] 36.1, 95% confidence interval [CI] 1.6–837.5, p = 0.03), and 7 days (HR 9.1, 1.1–79.2, p = 0.05), with a trend at 14 days (HR 4.6, 0.9–22.8, p = 0.06). Conclusions: Although only a minority of patients with symptomatic CS had a recurrent stroke within 14 days, early recurrent stroke risk was high, particularly within the first 72 hours. Earlier carotid revascularization or improved acute medical treatment may reduce recurrence in this high-risk group.

Background and Purpose— Reliable etiologic classification of ischemic stroke may enhance clinical trial design and identification of subtype-specific environmental and genetic risk factors. Although new classification systems (Causative Classification System [CCS] and ASCO [A for atherosclerosis, S for small vessel disease, C for cardiac source, O for other cause]) have been developed to improve subtype assignment, few comparative data exist from large studies. We hypothesized that both CCS and ASCO would reduce the proportion of patients classified as cause undetermined compared with the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) scheme in a large population-based stroke study. Methods— A single rater classified all first-ever ischemic strokes in the North Dublin Population Stroke Study, a population-based study of 294 529 North Dublin residents. Published algorithms for TOAST, CCS, and ASCO were applied. Results— In 381 first-ever ischemic stroke patients, CCS assigned fewer patients as cause undetermined (26.2% versus 39.4%; P P =0.004), large artery atherosclerosis (relative increase 44.1%; P =0.00006), small artery occlusion (relative increase 27.3%; P =0.00006), and other causes (relative increase 91.7%; P =0.001) compared with TOAST. When ASCO grade 1 evidence was applied, fewer patients were classified as small artery disease (relative decrease 29.1%; P =0.007) and more as large artery/atherothrombotic (relative increase 17.6%; P =0.03). ASCO grade 1 did not reduce the proportion of cause undetermined cases compared with TOAST (42.3% versus 39.4%; P =0.2). Agreement between systems ranged from good (κ=0.61 for TOAST/ASCO grade 1 small artery category) to excellent (κ=0.95 for TOAST/CCS and ASCO grade 1/CCS cardio/aorto-embolism category). Application of ASCO grades 1 to 3 indicated evidence of large artery/atherosclerosis (73.3%), cardio-embolism (31.3%), small artery (64.7%), and other cause (12%) in TOAST-undetermined cases. Conclusion— Both CCS and ASCO schemes showed good-to-excellent agreement with TOAST, but each had specific characteristics compared with TOAST for subtype assignment and data retention. The feasibility of a single combined classification system should be considered.

Background and Purpose— Transient ischemic attack (TIA) etiologic data and the ABCD 2 score may improve early stroke risk prediction, but studies are required in population-based cohorts. We investigated the external validity of the ABCD 2 score, carotid stenosis, and atrial fibrillation for prediction of early recurrent stroke after TIA. Methods— Patients with TIA in the North Dublin city population (N=294 529) were ascertained by using overlapping hospital and community sources. The relations between individual ABCD 2 items, carotid stenosis, atrial fibrillation, and early stroke were examined. Results— In confirmed TIA cases (n=443), carotid stenosis predicted 90-day stroke (hazard ratio=2.56; 95% CI, 1.27 to 5.15, P =0.003). Stroke risk rose with increasing grade of carotid stenosis, ranging from 5.4% (95% CI, 3.3% to 8.7%) with P =0.002). In confirmed TIA cases (n=443), the ABCD 2 score performed no better than chance for prediction of 90-day stroke ( c -statistic=0.55; 95% CI, 0.45 to 0.64), largely related to the 24.2% (8/33) of patients who experienced a recurrence and had low ABCD 2 scores (0–3). However, in nonspecialist-suspected TIA cases (n=700), the predictive utility improved for stroke at 28 ( c -statistic=0.61; 95% CI, 0.50 to 0.72) and 90 ( c -statistic=0.61; 95% CI, 0.52 to 0.71) days. Conclusions— In a population-based TIA cohort, significant predictive information was provided by carotid stenosis. The ABCD 2 score had predictive utility in patients with TIA suspected by nonspecialists. Low scores occurred in several patients with stroke recurrences, suggesting that caution is needed before using the score in isolation.

Background and Purpose— Transient ischemic attack (TIA) diagnosis is frequently difficult in clinical practice. Noncerebrovascular symptoms are often misclassified as TIA by nonspecialist physicians. Clinical prediction rules such as ABCD 2 improve the identification of patients with TIA at high risk of early stroke. We hypothesized that the ABCD 2 score may partly improve risk stratification due to improved discrimination of true TIA and minor ischemic stroke (MIS) from noncerebrovascular events. Methods— Consecutive patients with TIA were identified within a prospective population-based cohort study of stroke and TIA. The cohort was expanded by inclusion of patients with MIS and noncerebrovascular events referred to a daily TIA clinic serving the population. Diagnosis was assigned by a trained stroke physician independent of ABCD 2 score. Results— Five hundred ninety-four patients were included (292 [49.2%] TIA, 45 [7.6%] MIS, and 257 [43.3%] noncerebrovascular). The mean ABCD 2 score showed a graded increase across diagnostic groups (MIS mean 4.8 [SD 1.4] versus TIA mean 3.9 [SD 1.5] versus noncerebrovascular mean 2.9 [SD 1.5]; P 2 score discriminated well between noncerebrovascular and cerebrovascular events—TIA (c-statistic 0.68; 95% CI, 0.64 to 0.72), any vascular event (TIA+MIS; c-statistic 0.7; 95% CI, 0.66 to 0.74), and MIS (c-statistic 0.81; 95% CI, 0.75 to 0.87)—from noncerebrovascular events. Of ABCD 2 items, unilateral weakness (OR, 4.5; 95% CI, 3.1 to 6.6) and speech disturbance (OR, 2.5; 95% CI, 1.6, 4.1) were most likely overrepresented in TIA compared with noncerebrovascular groups. Conclusion— The ABCD 2 score had significant diagnostic usefulness for discrimination of true TIA and MIS from noncerebrovascular events, which may contribute to its predictive usefulness.

Introduction Accurate health economics data is essential for service planning and clinical guideline development. Stroke associated with atrial fibrillation (AF) is characteristically more severe and disabling than non-AF stroke. Few data exist on the economic impact of AF-stroke compared to non-AF-stroke in population-based samples. Methods The North Dublin Population Stroke Study is a population-based prospective study of incident stroke in Dublin, Ireland. Both direct (healthcare-related) and indirect costs were calculated over a 2-year post-stroke period for individual patients, using data for survival and disability, discharge destination, outpatient and family practitioner visits, community supports, and ongoing treatment. Acute inpatient care was costed using the casemix approach, measuring the resource use per hospitalization (index stroke plus post-stroke admissions). Length of stay was used to cost rehabilitation and nursing home admissions. Indirect costs of illness were calculated using in-hospital length of stay to determine loss of productivity. Total costs were compared for AF-stroke and non-AF stroke, calculated at 2007 prices and converted to US$ (2007 rates). Results Of 568 ischemic and hemorrhagic incident stroke patients, 31% (177) had AF-associated stroke. 2-year fatality was higher in AF-stroke patients (50.3% versus 35.1%, p=0.001). Total 2-year median cost was $34,982 for AF-stroke patients (25-75% IQR $14,213-$88,283) compared to median cost of $17,736 (25-75% IQR $10,803-45,838] in non-AF stroke patients (p Conclusion In this population study, AF-associated stroke was associated with substantially higher costs for hospitalisation and community support after discharge. With ageing populations and increasing stroke burden, AF-stroke is likely to account for an increasing proportion of overall cost to health services.

Background Symptomatic carotid stenosis is associated with a 3-fold risk of early stroke recurrence compared to other stroke subtypes. Current carotid imaging techniques rely on estimating plaque-related lumen narrowing but do not evaluate intra-plaque inflammation, a key mediator of plaque rupture and thromboembolism. Using combined 18 F-fluorodeoxyglucose positron emission tomography/CT (FDG-PET/CT) we investigated the relationship between inflammation-related FDG uptake and stroke recurrence. Methods Consecutive patients with a recent (median 6.5 days [IQR 4-8]) stroke, TIA, or retinal embolism and ipsilateral carotid stenosis ( ≥50%) were included. FDG uptake was quantified as mean standardised uptake values (SUV, g/ml). Patients were followed prospectively for stroke recurrence. Results 60 patients were included (25 stroke, 29 TIA, 6 retinal embolism). 22% (13/60) had stroke recurrence within 90 days. FDG uptake in ipsilateral carotid plaque was greater in patients with early recurrent stroke (mean SUV 1.85 [SD 0.44] vs. 1.58 [SD 0.32] g/ml, p=0.02). On life-table analysis, 90-day recurrence rates with mean SUV greater than a 2.14g/ml threshold were 80% (CI 41.8-99.2%) versus 22.9% (CI 12.3-40.3%) with SUV ≤2.14g/ml (log-rank p Conclusion In recently-symptomatic carotid stenosis, inflammation-related FDG uptake was associated with early stroke recurrence, independent of the degree of stenosis. Plaque FDG-PET may identify patients at highest risk for stroke recurrence, who may be selected for immediate revascularisation or intensive medical treatment.