Faculty Bibliography

The aim of the ICARO-3 study was to evaluate whether intra-arterial treatment, compared to intravenous thrombolysis, increases the rate of favourable functional outcome at 3 months in acute ischemic stroke and extracranial ICA occlusion. ICARO-3 was a non-randomized therapeutic trial that performed a non-blind assessment of outcomes using retrospective data collected prospectively from 37 centres in 7 countries. Patients treated with endovascular treatment within 6 h from stroke onset (cases) were matched with patients treated with intravenous thrombolysis within 4.5 h from symptom onset (controls). Patients receiving either intravenous or endovascular therapy were included among the cases. The efficacy outcome was disability at 90 days assessed by the modified Rankin Scale (mRS), dichotomized as favourable (score of 0-2) or unfavourable (score of 3-6). Safety outcomes were death and any intracranial bleeding. Included in the analysis were 324 cases and 324 controls: 105 cases (32.4 %) had a favourable outcome as compared with 89 controls (27.4 %) [adjusted odds ratio (OR) 1.25, 95 % confidence interval (CI) 0.88-1.79, p = 0.1]. In the adjusted analysis, treatment with intra-arterial procedures was significantly associated with a reduction of mortality (OR 0.61, 95 % CI 0.40-0.93, p = 0.022). The rates of patients with severe disability or death (mRS 5-6) were similar in cases and controls (30.5 versus 32.4 %, p = 0.67). For the ordinal analysis, adjusted for age, sex, NIHSS, presence of diabetes mellitus and atrial fibrillation, the common odds ratio was 1.15 (95 % IC 0.86-1.54), p = 0.33. There were more cases of intracranial bleeding (37.0 versus 17.3 %, p = 0.0001) in the intra-arterial procedure group than in the intravenous group. After the exclusion of the 135 cases treated with the combination of I.V. thrombolysis and I.A. procedures, 67/189 of those treated with I.A. procedures (35.3 %) had a favourable outcome, compared to 89/324 of those treated with I.V. thrombolysis (27.4 %) (adjusted OR 1.75, 95 % CI 1.00-3.03, p = 0.05). Endovascular treatment of patients with acute ICA occlusion did not result in a better functional outcome than treatment with intravenous thrombolysis, but was associated with a higher rate of intracranial bleeding. Overall mortality was significantly reduced in patients treated with endovascular treatment but the rates of patients with severe disability or death were similar. When excluding all patients treated with the combination of I.V. thrombolysis and I.A. procedures, a potential benefit of I.A. treatment alone compared to I.V. thrombolysis was observed.

BACKGROUND:QT dispersion (QTd) has been proposed as an indirect electrocardiography (ECG) measure of heterogeneity of ventricular repolarization. The predictive value of QTd in acute stroke remains controversial. We aimed to clarify the relationship between QTd and acute stroke and stroke prognosis. METHODS:A systematic review of the literature was performed using prespecified medical subjects heading terms, Boolean logic, and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Eligible studies included ischemic or hemorrhagic stroke and provided QTd measurements. RESULTS:Two independent reviewers identified 553 publications. Sixteen articles were included in the final analysis. There were a total of 888 stroke patients: 59% ischemic and 41% hemorrhagic. There was considerable heterogeneity in study design, stroke subtypes, ECG assessment time, control groups, and comparison groups. Nine studies reported a significant association between acute stroke and baseline QTd. Two studies reported that QTd increases are specifically related to hemorrhagic strokes, involvement of the insular cortex, right-side lesions, larger strokes, and increases in 3,4-dihydroxyphenylethylene glycol in hemorrhagic stroke. Three studies reported QTd to be an independent predictor of stroke mortality. One study each reported increases in QTd in stroke patients who developed ventricular arrhythmias and cardiorespiratory compromise. CONCLUSIONS:There are few well-designed studies and considerable variability in study design in addressing the significance of QTd in acute stroke. Available data suggest that stroke is likely to be associated with increased QTd. Although some evidence suggests a possible prognostic role of QTd in stroke, larger and well-designed studies need to confirm these findings.

BACKGROUND:Prior reports have linked both ischemic and hemorrhagic stroke to use of sympathomimetic drugs including phenylephrine. The purpose of this study is to describe the first case, to our knowledge of intracerebral hemorrhage (ICH) after oral use of phenylephrine and to systematically review the literature on phenylephrine and acute stroke. METHODS:A case report and review of the literature. RESULTS:A 59-year-old female presented with thunderclap headache, right hemiparesis, aphasia, and left gaze deviation. Head computed tomography (CT) showed a left frontal ICH with intraventricular and subarachnoid extension. She had no significant past medical history. For the previous 30 days, the patient was taking multiple common cold remedies containing phenylephrine to treat sinusitis. CT and magnetic resonance angiography showed no causative vascular abnormality. Catheter cerebral angiography supported reversible cerebral vasoconstriction syndrome (RCVS). Phenylephrine was determined to be the most likely etiology for her hemorrhage. A review of the literature, found 7 cases describing phenylephrine use with acute stroke occurrence: female, 5 of 7 (71%); route of administration, nasal (n = 3), ophthalmic (n = 2), intravenous (n = 1), intracorporeal injection (n = 1). Stroke types were subarachnoid hemorrhage (n = 5), ICH (n = 4), and ischemic (n = 1). One case reported RCVS after phenylephrine use. CONCLUSIONS:It is scientifically plausible that phenylephrine may cause strokes, consistent with the pharmacologic properties and adverse event profiles of similar amphetamine-like sympathomimetics. As RCVS has been well described in association with over-the-counter sympathomimetics, a likely, although not definitive, causal relationship between phenylephrine and ICH is proposed.

BACKGROUND AND PURPOSES/OBJECTIVE:This study aimed to identify clinical and ultrasound imaging predictors of progression of carotid luminal narrowing in subjects with asymptomatic moderate internal carotid artery (ICA) stenosis. METHODS:A total of 571 subjects with asymptomatic moderate (50-69%) ICA stenoses were enrolled. They underwent ultrasound examination at baseline and after 12 months. Demographics, vascular risk factors, medications, plaque characteristics (surface and echogenicity) and common carotid intima-media thickness (IMT) were collected. At the follow-up examination, any change of ICA stenosis was graded in three categories (i) ≥70% to near occlusion, (ii) near occlusion, and (iii) occlusion. Progression of stenosis was defined as an increase in the stenosis degree by at least one category from baseline to follow-up. RESULTS:At 12 months, progression occurred in 142 subjects (prevalence rate 25%). At the multivariable logistic model, pathological IMT values (considered as binary variable: normal: ≤1 mm vs. pathologic: >1 mm) significantly predicted the risk for plaque progression after adjusting the model for possible confounders (OR 2.28, 95% CI 1.18-4.43, P = .014, multivariable logistic model). CONCLUSIONS:Our results confirm the role of carotid wall thickening as a marker of atherosclerosis. Carotid IMT measurement should be considered to implement risk stratification in patients with asymptomatic carotid disease.

We sought to investigate potential racial disparities in early outcomes of young individuals with stroke in an international multicenter study. We evaluated consecutive patients with first-ever acute stroke aged 18-45 years from prospective databases involving 12 tertiary-care stroke centers in North America (n = 2), Europe (n = 6), and Asia (n = 4). Demographics, vascular risk factors, stroke subtypes, pre-stroke functional status, stroke severity, blood pressure parameters, and serum glucose at hospital admission were documented. The outcome events of interest were 30-day mortality and 30-day favorable functional outcome (FFO) defined as modified-Rankin Scale score of 0-1. A total of 1,134 young adults (mean age 37.4 ± 7.0 years; 58.8 % men; 48.6 % Whites, 23.9 % Blacks, and 27.5 % Asians; median baseline National Institutes of Health Stroke Scale score 6 points, interquartile range 2-13) were included in the analyses. The 30-day stroke mortality and FFO rates differed (p < 0.001) across races. After adjusting for potential confounders, race was independently associated with 30-day mortality (p = 0.026) and 30-day FFO (p = 0.035). Blacks had a fourfold higher odds of 30-day stroke mortality in comparison to Asians (OR 4.00; 95 % CI 1.38-11.59; p = 0.011). Whites also had an increased likelihood of 30-day stroke mortality in comparison to Asians (OR 3.59; 95 % CI 1.28-10.03; p = 0.015). Blacks had a lower odds of 30-day FFO in comparison to Whites (OR 0.57; 95 % CI 0.35-0.91; p = 0.018). Racial disparities in early outcomes following first-ever stroke in young individuals appear to be independent of other known outcome predictor variables. Whites appear to have higher likelihood of 30-day FFO and Asians have lower odds of 30-day stroke mortality.

BACKGROUND AND PURPOSE/OBJECTIVE:This study aimed to monitor cognitive performance during a 3-year period in subjects with bilateral asymptomatic severe internal carotid artery stenosis and to explore the role of cerebral hemodynamics and atherosclerotic disease in the development of cognitive dysfunction. METHODS:One hundred fifty-nine subjects with bilateral asymptomatic severe internal carotid artery stenosis were included and prospectively evaluated for a 3-year period. At entry, demographics, vascular risk profile, and pharmacological treatments were defined. Cognitive status was evaluated using the Mini-Mental State Examination at baseline and at follow-up. Cerebral hemodynamics was assessed by transcranial Doppler-based breath-holding index test. As a measure of the extent of systemic atherosclerotic disease, common carotid artery intima-media thickness was measured. A cutoff for pathological values was set at 0.69 for breath-holding index and 1.0 mm for intima-media thickness. RESULTS:The risk of decreasing in Mini-Mental State Examination score increased progressively from patients with bilaterally normal to those with unilaterally abnormal breath-holding index, reaching the highest probability in patients with bilaterally abnormal breath-holding index (P<0.0001). Pathological values of intima-media thickness did not influence the risk of Mini-Mental State Examination score change. CONCLUSIONS:Our findings suggest that patients with asymptomatic bilateral severe internal carotid artery stenosis may be at risk of developing cognitive impairment. The evaluation of the hemodynamic status, besides providing insights about the possible mechanism behind the cognitive dysfunction present in carotid atherosclerotic disease, may be of help for the individuation of subjects deserving earlier and more aggressive treatments.

PURPOSE/OBJECTIVE:The aim of this study was to evaluate the relationship between arterial blood pressure (BP) variability during the acute phase and the 3-month outcome in ischemic stroke patients with internal carotid artery (ICA) occlusion. METHODS:At least 10 BP measurements during the first 48 h after stroke onset were obtained in 89 patients with ICA occlusion. BP profile was described using various parameters: average of recordings, maximum (max), minimum (min), difference between max and min (max-min), standard deviation (SD) and coefficient of variation (CV) for both systolic and diastolic BP. Outcome at 3 months was defined using the modified Rankin Scale (mRS) score corrected for baseline stroke severity. RESULTS:Fifty-five patients had a good and 34 a poor outcome. Max values, max-min, SD and CV of both systolic and diastolic BP resulted significantly higher in patients with poor outcome compared to those with good outcome (p<0.05, multivariate adjusted model). CONCLUSIONS:In a cohort of acute ischemic stroke patients with ipsilateral ICA occlusion BP variability, assessed in the acute phase, was associated with poor clinical outcome. These preliminary exploratory findings are worthy of further study to be conducted to confirm or confute the role of BP variability in predicting stroke outcome. In order to obtain more comprehensive information, it would also be appropriate to consider the possibility of acquiring data related to the pathophysiology of stroke and to cerebral hemodynamic changes.

BACKGROUND:Recently, a strategy for treating stroke directly at the emergency site was developed. It was based on the use of an ambulance equipped with a scanner, a point-of-care laboratory, and telemedicine capabilities (Mobile Stroke Unit). Despite demonstrating a marked reduction in the delay to thrombolysis, this strategy is criticized because of potentially unacceptable costs. METHODS:We related the incremental direct costs of prehospital stroke treatment based on data of the first trial on this concept to one year direct cost savings taken from published research results. Key parameters were configuration of emergency medical service personnel, operating distance, and population density. Model parameters were varied to cover 5 different relevant emergency medical service scenarios. Additionally, the effects of operating distance and population density on benefit-cost ratios were analyzed. RESULTS:Benefits of the concept of prehospital stroke treatment outweighed its costs with a benefit-cost ratio of 1.96 in the baseline experimental setting. The benefit-cost ratio markedly increased with the reduction of the staff and with higher population density. Maximum benefit-cost ratios between 2.16 and 6.85 were identified at optimum operating distances in a range between 43.01 and 64.88 km (26.88 and 40.55 miles). Our model implies that in different scenarios the Mobile Stroke Unit strategy is cost-efficient starting from an operating distance of 15.98 km (9.99 miles) or from a population density of 79 inhabitants per km2 (202 inhabitants per square mile). CONCLUSION/CONCLUSIONS:This study indicates that based on a one-year benefit-cost analysis that prehospital treatment of acute stroke is highly cost-effective across a wide range of possible scenarios. It is the highest when the staff size of the Mobile Stroke Unit can be reduced, for example, by the use of telemedical support from hospital experts. Although efficiency is positively related to population density, benefit-cost ratios can be greater than 1 even in rural settings.

INTRODUCTION/BACKGROUND:With a view to develop an operator-independent monitoring system for sonothrombolysis, we aimed to evaluate the per cent agreement of power motion transcranial Doppler vessel tracks compared with computed tomography angiography in identification of the anterior and posterior circulation vessels in patients with acute ischaemic stroke. METHODS:Consecutive acute ischaemic stroke patients who underwent emergent brain computed tomography angiography and bedside power motion transcranial Doppler were studied. Depth ranges for detecting anterior and posterior circulation vessels were derived from power motion transcranial Doppler flow tracks and computed tomography angiography images of the circle of Willis. We calculated percent agreement of power motion transcranial Doppler with computed tomography angiography for the anterior and posterior circulation vessel localization using computed tomography angiography as reference. RESULTS:Samples were obtained from 34 acute ischaemic stroke patients (mean age 61 ± 16 years, 62% men, median National Institutes of Health Stroke Scale (NIHSS) score 5, interquartile range 2-8). A total of 229 Power motion Doppler computed tomography angiography vessel pairs were analysed. Power motion transcranial Doppler tracks for M1 and proximal M2 middle cerebral artery (MCA) were located at 24-68 mm (M1 MCA: 36-68 mm; M2 MCA: 24-53 mm); anterior cerebral artery (ACA): 50-78 mm; P1 posterior cerebral artery (PCA): 50-74 mm; left vertebral artery: 30-74 mm; right vertebral artery: 30-78 mm; basilar artery: 76-106 mm. The per cent agreement of power motion Doppler-transcranial Doppler for identifying proximal intracranial arteries compared to computed tomography angiography was: M1 and M2 MCA: 100% (95% confidence interval: 96-100%); M1 MCA: 98% (95% confidence interval: 86-100%); M2 MCA: 94% (95% confidence interval: 79-99%); A1 ACA: 82% (95% confidence interval: 68-91%); P1 PCA: 70% (95% confidence interval: 53-83%); left vertebral artery: 96% (95% confidence interval: 80-100%); right vertebral artery: 96% (95% confidence interval: 79-100%); basilar artery: 100% (95% confidence interval: 89-100%). CONCLUSIONS:Power motion transcranial Doppler intercepts proximal vessels with good-to-excellent agreement with computed tomography angiography. Depth ranges (as opposed to average depths) can be used to target intracranial arterial segments for sonothrombolysis.