Structural and Functional Characteristics of Cerebral Arteries as an Explanation for Clinical Syndromes Limited to the Brain.

Vascular disease affects many different arterial beds throughout the body. Yet the brain is susceptible to several vascular disorders that either are not found in other parts of the body or when found are much less likely to cause clinical syndromes in other organs. This specific vulnerability of the brain may be explained by structural and functional differences between the vessels of the brain and those of vessels in other parts of the body. In this review, we focus on how cerebrovascular anatomy and physiology may make the brain and its vessels more susceptible to unique vascular pathologies. To highlight these differences, we use our knowledge of five diseases and syndromes that most commonly manifest in the intracranial vasculature. For each, we identify characteristics of the intracranial arteries that make them susceptible to these diseases, while noting areas of uncertainty requiring further research.

Stroke Care during the COVID-19 Pandemic: International Expert Panel Review.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has placed a tremendous strain on healthcare services. This study, prepared by a large international panel of stroke experts, assesses the rapidly growing research and personal experience with COVID-19 stroke and offers recommendations for stroke management in this challenging new setting: modifications needed for prehospital emergency rescue and hyperacute care; inpatient intensive or stroke units; posthospitalization rehabilitation; follow-up including at-risk family and community; and multispecialty departmental developments in the allied professions. SUMMARY: The severe acute respiratory syndrome coronavirus 2 uses spike proteins binding to tissue angiotensin-converting enzyme (ACE)-2 receptors, most often through the respiratory system by virus inhalation and thence to other susceptible organ systems, leading to COVID-19. Clinicians facing the many etiologies for stroke have been sobered by the unusual incidence of combined etiologies and presentations, prominent among them are vasculitis, cardiomyopathy, hypercoagulable state, and endothelial dysfunction. International standards of acute stroke management remain in force, but COVID-19 adds the burdens of personal protections for the patient, rescue, and hospital staff and for some even into the postdischarge phase. For pending COVID-19 determination and also for those shown to be COVID-19 affected, strict infection control is needed at all times to reduce spread of infection and to protect healthcare staff, using the wealth of well-described methods. For COVID-19 patients with stroke, thrombolysis and thrombectomy should be continued, and the usual early management of hypertension applies, save that recent work suggests continuing ACE inhibitors and ARBs. Prothrombotic states, some acute and severe, encourage prophylactic LMWH unless bleeding risk is high. COVID-19-related cardiomyopathy adds risk of cardioembolic stroke, where heparin or warfarin may be preferable, with experience accumulating with DOACs. As ever, arteritis can prove a difficult diagnosis, especially if not obvious on the acute angiogram done for clot extraction. This field is under rapid development and may generate management recommendations which are as yet unsettled, even undiscovered. Beyond the acute management phase, COVID-19-related stroke also forces rehabilitation services to use protective precautions. As with all stroke patients, health workers should be aware of symptoms of depression, anxiety, insomnia, and/or distress developing in their patients and caregivers. Postdischarge outpatient care currently includes continued secondary prevention measures. Although hoping a COVID-19 stroke patient can be considered cured of the virus, those concerned for contact safety can take comfort in the increasing use of telemedicine, which is itself a growing source of patient-physician contacts. Many online resources are available to patients and physicians. Like prior challenges, stroke care teams will also overcome this one. Key Messages: Evidence-based stroke management should continue to be provided throughout the patient care journey, while strict infection control measures are enforced.

The Role of Hemorrhagic Transformation in Acute Ischemic Stroke Upon Clinical Complications and Outcomes.

BACKGROUND AND PURPOSE: Hemorrhagic transformation (HT) is a common neurological complication after ischemic stroke. The influence of symptomatic HT upon clinical outcomes post-stroke is well established, however, the role of asymptomatic HT upon prognosis is still unclear. We aimed to analyze the relationship between HT, clinical complications and outcomes in patients not submitted to reperfusion therapies (RT). METHODS: We included 448 randomly selected patients admitted with acute ischemic stroke to a tertiary hospital stroke unit from 2015 to 2017. Patients submitted to RT were excluded. All patients were evaluated with computed tomography (CT) at admission and within 7 days from the initial CT. Patients with HT were divided into two groups: symptomatic and asymptomatic cases based on the ECASS II definition. A good clinical outcome was defined as a modified Rankin Scale (mRS) 0-2 at discharge. RESULTS: A total of 95 patients (21.2%) had HT (51 asymptomatic and 44 symptomatic). Age, NIHSS at admission and symptomatic HT were associated with a higher risk of developing pneumonia and seizures during hospitalization. Symptomatic HT was also associated with a prolonged length of hospitalization and death and inversely associated with good clinical outcomes at discharge (OR 0.96, 95% CI 0.94-0.98, p<0.001). In an adjusted analysis, even asymptomatic HT was independently associated with worse clinical outcomes at discharge (mRS 4-6) (OR 5.99, 95% CI 1.83-19.58, p = 0.003). CONCLUSIONS: Symptomatic HT is associated with a higher risk of clinical complications, prolonged hospitalization, death and worse clinical outcome at discharge. Furthermore, even patients with asymptomatic HT had a higher chance of worse clinical outcomes at discharge.

Predicting hemorrhagic transformation in patients not submitted to reperfusion therapies.

BACKGROUND: Well studied in patients with ischemic stroke after reperfusion therapies (RT), hemorrhagic transformation (HT) is also common in patients not treated with RT and can lead to disability even in initially asymptomatic cases. The best predictors of HT in patients not treated with RT are not well established. Therefore, we aimed to identify predictors of HT in patients not submitted to RT and create a user-friendly predictive score (PROpHET). MATERIAL AND METHODS: Patients admitted to a Comprehensive Stroke Center from 2015 to 2017 were prospectively evaluated and randomly selected to the derivation cohort. A multivariable logistic regression modeling was built to produce a predictive grading score for HT. The external validation was assessed using datasets from 7 Comprehensive Stroke Centers using the area under the receiver operating characteristic curve (AUROC). RESULTS: In the derivation group, 448 patients were included in the final analysis. The validation group included 2,683 patients. The score derived from significant predictors of HT in the multivariate logistic regression analysis was male sex (1 point), ASPECTS ≤ 7 (2 points), presence of leukoaraiosis (1 point), hyperdense cerebral middle artery sign (1 point), glycemia at admission ≥180 mg/dL (1 point), cardioembolism (1 point) and lacunar syndrome (-3 points) as a protective factor. The grading score ranges from -3 to 7. A Score ≥3 had 78.2% sensitivity and 75% specificity, and AUROC of 0.82 for all cases of HT. In the validation cohort, our score had an AUROC of 0.83. CONCLUSIONS: The PROpHET is a simple, quick, cost-free, and easy-to-perform tool that allows risk stratification of HT in patients not submitted to RT. A cost-free computerized version of our score is available online with a user-friendly interface.

Histopathological Differences Between the Anterior and Posterior Brain Arteries as a Function of Aging.

BACKGROUND AND PURPOSE: We tested the hypothesis that posterior brain arteries differ pathologically from anterior brain arteries and that this difference varies with age. METHODS: Brain large arteries from 194 autopsied individuals (mean age 56±17 years, 63% men, 25% nonwhite, 17% with brain infarcts) were analyzed to obtain the areas of arterial layers and lumen as well as the relative content of elastin, collagen, and amyloid. Visual rating was used to determine the prevalence of atheroma, calcification, vasa vasorum, pattern of intima thickening, and internal elastic lamina gaps. We used multilevel models adjusting for age, sex, ethnicity, vascular risk factors, artery type and location, and multiple comparisons. RESULTS: Of 1362 large artery segments, 5% had vasa vasorum, 5% had calcifications, 15% had concentric intimal thickening, and 11% had atheromas. Posterior brain arteries had thinner walls, less elastin, and more concentric intima thickening than anterior brain arteries. Compared to anterior brain arteries, the basilar artery had higher arterial area encircled by the internal elastic lamina, whereas the vertebral arteries had higher prevalence of elastin loss, concentric intima thickening, and nonatherosclerotic stenosis. In younger individuals, vertebral artery calcifications were more likely than calcification in anterior brain arteries, but this difference attenuated with age. CONCLUSIONS: Posterior brain arteries differ pathologically from anterior brain arteries in the degree of wall thickening, elastin loss, and concentric intimal thickening.

Resting Heart Rate and Ischemic Stroke in Patients with Heart Failure.

BACKGROUND: Although high resting heart rate (RHR) is known to be associated with an increased risk of mortality and hospital admission in patients with heart failure, the relationship between RHR and ischemic stroke remains unclear. This study is aimed at investigating the relationship between RHR and ischemic stroke in patients with heart failure in sinus rhythm. METHODS: We examined 2,060 patients with systolic heart failure in sinus rhythm from the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction trial. RHR was determined from baseline electrocardiogram, and was examined as both a continuous variable and a categorical variable using quartiles. Ischemic strokes were identified during follow-up and adjudicated by physician review. RESULTS: During 3.5 ± 1.8 years of follow-up, 77 patients (5.3% from Kaplan-Meier [KM] curve) experienced an ischemic stroke. The highest incidence of ischemic stroke (21/503 [KM 6.9%]) was observed in the lowest RHR quartile (RHR <64 beats/min) compared to other groups; 22/573 (KM 5.3%) in 64-70 beats/min, 13/465 (KM 3.5%) in 71-79 beats/min, and 21/519 (KM 5.4%) in RHR >79 beats/min (p = 0.693). Multivariable Cox proportional hazards analysis revealed that RHR was significantly associated with ischemic stroke (hazard ratio per unit decrease: 1.07, 95% CI 1.02-1.13, when RHR <64/beats/min; p = 0.038), along with a history of stroke or transient ischemic attack and left ventricular ejection fraction. CONCLUSIONS: In contrast to its beneficial effect on mortality and hospital re-admissions, lower RHR may increase the risk of ischemic stroke in patients with systolic heart failure in sinus rhythm.

Clinical and Echocardiographic Factors Associated With New-Onset Atrial Fibrillation in Heart Failure　- Subanalysis of the WARCEF Trial.

BACKGROUND: Heart failure (HF) patients have a high incidence of new-onset AF. Given the adverse prognostic influence of AF in HF, identifying patients at high risk of developing AF is important. METHODS AND RESULTS: The incidence and factors associated with new-onset AF were investigated in patients in sinus rhythm with reduced LVEF enrolled in the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial. Analyses involved clinical factors alone (n=2,219), and clinical plus echocardiographic findings (n=1,125). During 3.5±1.8 years of follow-up, 212 patients (9.6% of total cohort) developed AF. In both samples, new-onset AF was associated with age, male sex, White race, and IHD. Among echocardiographic variables, only LAD predicted AF. On multivariate Cox modeling, age (HR, 1.02; 95% CI: 1.00-1.03, P=0.008), IHD (HR, 1.37; 95% CI: 1.02-1.84, P=0.036) and LAD (HR, 1.48; 95% CI: 1.15-1.91, P=0.003) remained associated with AF onset. Patients with IHD, LAD>4.5 cm and age>50 years had a 2.5-fold higher risk of AF than patients without any of these characteristics (HR, 2.52; 95% CI: 1.72-3.69, P<0.0001). CONCLUSIONS: Age, IHD and LAD independently predict new-onset AF in HF patients in sinus rhythm, at younger age and smaller LAD than generally believed. This information may be useful to risk-stratify HF patients for AF development, allowing close monitoring and possibly early detection. (Circ J 2016; 80: 619-626).

Antiphospholipid Antibodies and Recurrent Thrombotic Events: Persistence and Portfolio.

BACKGROUND: There are very limited prospective data on the significance of persistent antiphospholipid antibodies (aPL) and recurrent thrombo-occlusive events (TOEs). We investigated the prognostic value of (1) 2 newer aPL assays, (2) an aPL portfolio and (3) persistent aPL positivity following stroke. METHODS: A total of 1,770 subjects from the APASS-WARSS study underwent further aPL testing for antibodies to phosphatidylserine (aPS) and anti-ß2-glycoprotein-I (anti-ß2GPI) from stored sera. Follow-up aPL status was also tested in a subset of subjects. Primary analysis was based on time to any TOE (ischemic stroke, myocardial infarction, transient ischemic attack, deep vein thrombosis, pulmonary embolism or systemic arterial occlusion)/death at 2 years. Cox proportional hazard analyses assessed whether aPL independently related to outcome. RESULTS: Persistent anti-ß2GPI decreased the time to TOE/death after adjustment for potential confounders (hazards ratio (HR) 2.86, 95% CI 1.21-6.76, p = 0.017). When persistent anti-ß2GPI was combined with another persistently positive aPL, time to TOE/death was also reduced (HR 3.79, 95% CI 1.18-12.14, p = 0.025). Neither persistent anticardiolipin antibodies nor persistent aPS alone nor a single positive anti-ß2GPI nor aPS was associated with decreased time to TOE/death. No single positive aPL, portfolio of baseline aPL or any persistent aPL increased the rate of TOE/death. CONCLUSIONS: Rates of TOE/death were not influenced by aPL results at baseline or follow-up. Persistent anti-ß2GPI alone, and with persistent second aPL, was independently associated with decreased time to TOE/death. Persistent aPL, an aPL portfolio and newer aPL in ischemic stroke patients are not helpful in predicting an increased rate of recurrent TOEs.

Recurrent stroke in the warfarin versus aspirin in reduced cardiac ejection fraction (WARCEF) trial.

BACKGROUND AND PURPOSE: WARCEF randomized 2,305 patients in sinus rhythm with ejection fraction (EF) ≤ 35% to warfarin (INR 2.0-3.5) or aspirin 325 mg. Warfarin reduced the incident ischemic stroke (IIS) hazard rate by 48% over aspirin in a secondary analysis. The IIS rate in heart failure (HF) is too low to warrant routine anticoagulation but epidemiologic studies show that prior stroke increases the stroke risk in HF. In this study, we explore IIS rates in WARCEF patients with and without baseline stroke to look for risk factors for IIS and determine if a subgroup with an IIS rate high enough to give a clinically relevant stroke risk reduction can be identified. METHODS: We compared potential stroke risk factors between patients with baseline stroke and those without using the exact conditional score test for Poisson variables. We looked for risk factors for IIS, by comparing IIS rates between different risk factors. For EF we tried cut-off points of 10, 15 and 20%. The cut-off point 15% was used as it was the highest EF that was associated with a significant increase in IIS rate. IIS and EF strata were balanced as to warfarin/aspirin assignment by the stratified randomized design. A multiple Poisson regression examined the simultaneous effects of all risk factors on IIS rate. IIS rates per hundred patient years (/100 PY) were calculated in patient groups with significant risk factors. Missing values were assigned the modal value. RESULTS: Twenty of 248 (8.1%) patients with baseline stroke and 64 of 2,048 (3.1%) without had IIS. IIS rate in patients with baseline stroke (2.37/100 PY) was greater than patients without (0.89/100 PY) (rate ratio 2.68, p < 0.001). Fourteen of 219 (6.4%) patients with ejection fraction (EF) <15% and 70 of 2,079 (3.4%) with EF ≥ 15% had IIS. In the multiple regression analysis stroke at baseline (p < 0.001) and EF <15% vs. ≥ 15% (p = 0.005) remained significant predictors of IIS. IIS rate was 2.04/100 PY in patients with EF <15% and 0.95/100 PY in patients with EF ≥ 15% (p = 0.009). IIS rate in patients with baseline stroke and reduced EF was 5.88/100 PY with EF <15% decreasing to 2.62/100 PY with EF <30%. CONCLUSIONS: In a WARCEF exploratory analysis, prior stroke and EF <15% were risk factors for IIS. Further research is needed to determine if a clinically relevant stroke risk reduction is obtainable with warfarin in HF patients with prior stroke and reduced EF.

Acute cervical myelopathy due to presumed fibrocartilaginous embolism: a case report and systematic review of the literature.

INTRODUCTION: Fibrocartilaginous embolism (FCE) is an uncommon cause of myelopathy that should be considered after more common causes have been ruled out. OBJECTIVE: This article presents a case report of a 50-year-old man with acute myelopathy attributed to FCE and summarizes the clinical features of the disease by analyzing all of the published evidence. DATA SOURCES AND EXTRACTION: Two computerized literature searches (MEDLINE-Pubmed, EMBASE, the Cochrane Library) were performed. The search term used was "Fibrocartilaginous embolism." No language restrictions were applied. All articles were evaluated and key data were extracted according to predefined criteria: patient's age, year of publication, localization of the embolism and type of vascular syndrome, clinical outcome, and time to death in the fatal cases. RESULTS: Fifty-two cases (39 biopsy proven and 13 clinically diagnosed) were found in the literature. Median age at presentation was 37 years (interquartile range, 19-53) and 56% were women. Median progression of symptoms was 6 hours (interquartile range, 5-60 h), predominantly affecting the cervical spine (48%) by an arterial embolic source (56%). CONCLUSIONS: FCE is an unusual cause of spinal cord and cerebral ischemia with unknown incidence. Implementation of diagnostic imaging techniques and initial management of acute spinal disorders care in intensive care units might increase the incidence of disease antemortem. FCE should be considered in the differential diagnosis of ischemic spinal cord injury when no other causes can be identified and especially when the onset is progressive over several hours.

Efficacy and safety of vorapaxar in patients with prior ischemic stroke.

BACKGROUND AND PURPOSE: Vorapaxar is an antiplatelet agent that antagonizes thrombin-mediated activation of the protease-activated receptor-1 on platelets. We tested the efficacy and safety of vorapaxar in a prespecified analysis in the stroke subcohort from a multinational, randomized, placebo-controlled trial. METHODS: We randomly assigned patients with prior atherothrombosis (myocardial infarction, peripheral artery disease, or ischemic stroke) to receive vorapaxar (2.5 mg daily) or placebo added to standard antiplatelet therapy. Patients who qualified with stroke (N=4883) had a history of ischemic stroke in the prior 2 weeks to 12 months. The primary end point was the composite of cardiovascular death, myocardial infarction, or any stroke. RESULTS: The qualifying stroke was classified as large vessel in 35%, small vessel in 47%, and other/unknown in 18%. In the stroke cohort, cardiovascular death, myocardial infarction, or stroke through 3 years was not reduced with vorapaxar versus placebo (13.0% vs 11.7%; hazard ratio, 1.03; 95% confidence interval, 0.85-1.25), including recurrent ischemic stroke (hazard ratio, 0.99; 95% confidence interval, 0.78-1.25). There were no significant differences in the effect of vorapaxar based on the type or timing of the qualifying stroke. Intracranial hemorrhage at 3 years was increased with vorapaxar (2.5% vs 1.0%; hazard ratio, 2.52; 95% confidence interval, 1.46-4.36). CONCLUSIONS: In patients with prior ischemic stroke who receive standard antiplatelet therapy, adding vorapaxar increased the risk of intracranial hemorrhage without an improvement in major vascular events, including ischemic stroke. These findings add to the accumulating evidence establishing important risks with combination antiplatelet therapy in patients with prior stroke. Clinical Trial Registration Information- http://www.clinicaltrials.gov. Unique identifier: NCT00526474.

In-Hospital Aspirin Dose as a Risk Factor for Hemorrhagic Transformation in Patients Not Treated With Thrombolysis.

BACKGROUND: Aspirin is widely used as secondary prophylaxis for acute ischemic stroke. However, its influence on the risk of spontaneous hemorrhagic transformation (HT) is still unclear. Predictive scores of HT have been proposed. We hypothesized that an increased aspirin dose might be harmful in patients at a high risk of HT. This study aimed to analyze the relationship between in-hospital daily aspirin dose (IAD) and HT in patients with acute ischemic stroke. METHODS: We conducted a retrospective cohort study of patients admitted to our comprehensive stroke center between 2015 and 2017. The attending team defined IAD. All included patients underwent either computed tomography or magnetic resonance imaging within 7 days of admission. The risk of HT was assessed using the predictive score of HT in patients not undergoing reperfusion therapies. Regression models were used to evaluate the correlations between HT and IAD. RESULTS: A total of 986 patients were included in the final analysis. The prevalence of HT was 19.2%, and parenchymatous hematomas type-2 (PH-2) represented 10% (n=19) of these cases. IAD was not associated with HT ( P =0.09) or PH-2 ( P =0.06) among all patients. However, in patients at a higher risk for HT (patients not undergoing reperfusion therapies ≥3), IAD was associated with PH-2 (odds ratio 1.01,95% CI 1.001-1.023, P =0.03) in an adjusted analysis. Taking 200 versus 300 mg aspirin was protective against PH-2 (odds ratio 0.102, 95% CI 0.018-0.563, P =0.009). CONCLUSION: An increased in-hospital aspirin dose is associated with intracerebral hematoma in patients at a high risk of HT. Stratifying the risk of HT may lead to individualized daily aspirin dose choices. However, clinical trials on this topic are required.

Predictors of congruency between clinical and radiographic Oxfordshire Community Stroke Project Classification subtypes.

BACKGROUND: The Oxfordshire Community Stroke Project (OCSP) classification has been widely used to assess ischemic stroke patients based on clinical characteristics alone. However, the correlation between the clinical presentation evaluated using OCSP and imaging findings is yet to be determined. Our study aimed to describe the baseline characteristics of the OCSP subtypes of patients admitted with ischemic stroke and evaluate the predictors of the relationship between clinical and neuroimaging findings. METHODS: Patients with a confirmed diagnosis of ischemic stroke admitted to a comprehensive stroke center in Brazil between February 2015 and October 2017 were eligible for the study. All participants underwent computed tomography (CT) at admission and follow-up neuroimaging within seven days, per the institutional protocol. Trained staff classified patients according to the OCSP at hospital admission. The radiographic OCSP classification was retrospectively assessed based on the last follow-up neuroimaging by investigators unaware of the clinical classification. RESULTS: The overall agreement rates ranged from 65.5% to 88.7%. Lower NIHSS scores, absent hyperdense MCA sign, higher ASPECTS, and absent brainstem symptoms were related to a higher risk of misclassification. Treatment with intravenous tPA was associated with reclassification in patients with total anterior circulation syndrome. For predicting radiographic posterior circulation involvement, vertigo (OR 2.9, 95% CI 1.7-5.1, p < 0.001) and brainstem symptoms (OR 35, 95% CI 20.5-60.2, p < 0.001) were directly associated with correct classification, but motor and higher cerebral function were not correlated. CONCLUSION: The clinical OCSP classification presented good congruency rates with the neuroimaging findings. However, patients with lacunar syndromes are often misclassified when radiological criteria are considered.

Predictors of hemorrhagic transformation differences between patients treated or not with reperfusion therapy.

BACKGROUND: Hemorrhagic transformation (HT) is a dreaded complication in stroke patients who were treated or not with recombinant tissue plasminogen activator (tPA). There are many predictive scores of HT, but all of them included patients treated with tPA. Molecular effects of tPA and clinical aspects of eligible patients for tPA therapy may imply specific HT's risk factors. We aimed to describe HT's characteristics and risk factors in patients treated or not with tPA. METHODS: We included 1565 consecutive stroke patients admitted to a Comprehensive Stroke Center, from 2015 to 2017. All included patients underwent a follow-up neuroimaging within seven days after admission. From a logistic regression model, we derived a score based on the beta-coefficients. The accuracy of the models was attested by Receiver Operating Characteristic analysis. RESULTS: Low ASPECTS, blood glucose ≥ 180 mg/dL, tPA treatment, and cardio-aortic embolism were predictors of HT. Male sex, leukoaraiosis, and hyperdense MCA sign were associated with HT in non-treated patients. Diastolic blood pressure ≥ 105 mmHg was a risk factor only in non-treated patients. The cutoff of our predictive score of HT was higher in patients not treated with tPA (5 vs 2 points). CONCLUSIONS: High arterial blood pressure was associated with HT only in patients treated with tPA. Different cutoffs and accuracy measurements suggest that scoring systems derived from patients treated with tPA may not be efficient to predict HT in non-treated patients. Further directions indicate considering the use of reperfusion therapies to select the most accurate predictive variables of HT.

Predicting hemorrhagic transformation in posterior circulation stroke patients not treated with reperfusion therapies.

INTRODUCTION: Posterior Circulation (PC) stroke represents one-fifth of all ischemic strokes, with peculiar physiological characteristics. Hemorrhagic Transformation (HT) is a dreaded complication among stroke patients. Many predictive scores of this complication have been proposed, but none is designed specifically for PC stroke patients - therefore, patients who are not eligible for reperfusion therapies (RT) represent about 80% of hospitalized cases. We propose a scoring system to assess the HT risk in PC stroke patients not submitted to RT. METHODS: We retrospectively evaluated data of patients diagnosed with PC stroke not treated with RT from 5 Comprehensive Stroke Centers (four in Brazil, 1 in the US) from 2015 to 2018. All patients underwent CT scan or MRI at admission and a follow-up neuroimaging within seven days. Independent variables identified in a logistic regression analysis were used to produce a predictive grading score. RESULTS: We included 952 patients in the final analysis. The overall incidence of HT was 8.7%. Male gender (1 point), NIH Stroke Scale at admission ≥ 5 points (1), blood glucose at admission ≥ 160 mg/dL (1), and cardioembolism (2) were independently associated with HT. The AUC of the grading score (0 to 5 points) was 0.713 (95% CI 0.65-0.78). Subjects with a score ≥ 3 points had an OR of 4.8 (95% CI 2.9-7.9, p < 0.001) for HT. CONCLUSIONS: Our score has good accuracy in identifying patients at higher risk of HT. This score may be useful for evaluating secondary prevention and stratifying patients in the context of even clinical trials.

Oxfordshire Community Stroke Project Classification: A proposed automated algorithm.

INTRODUCTION: The Oxfordshire Community Stroke Project (OCSP) proposed a clinical classification for Stroke patients. This classification has proved helpful to predict the risk of neurological complications. However, the OCSP was initially based on findings on the neurological assesment, which can pose difficulties for classifying patients. We aimed to describe the development and the validation step of a computer-based algorithm based on the OCSP classification. MATERIALS AND METHODS: A flow-chart was created which was reviewed by five board-certified vascular neurologists from which a computer-based algorithm (COMPACT) was developed. Neurology residents from 12 centers were invited to participate in a randomized trial to assess the effect of using COMPACT. They answered a 20-item questionnaire for classifying the vignettes according to the OCSP classification. Each correct answer has been attributed to 1-point for calculating the final score. RESULTS: Six-two participants agreed to participate and answered the questionnaire. Thirty-two were randomly allocated to use our algorithm, and thirty were allocated to adopt a list of symptoms alone. The group who adopted our algorithm had a median score of correct answers of 16.5[14.5, 17]/20 versus 15[13, 16]/20 points, p = 0.014. The use of our algorithm was associated with the overall rate of correct scores (p = 0.03). DISCUSSION: Our algorithm seemed a useful tool for any postgraduate year Neurology resident. A computer-based algorithm may save time and improve the accuracy to classify these patients. CONCLUSION: An easy-to-use computer-based algorithm improved the accuracy of the OCSP classification, with the possible benefit of further improvement of the prediction of neurological complications and prognostication.

Medical management with interventional therapy versus medical management alone for unruptured brain arteriovenous malformations (ARUBA): final follow-up of a multicentre, non-blinded, randomised controlled trial.

BACKGROUND: In A Randomized trial of Unruptured Brain Arteriovenous malformations (ARUBA), randomisation was halted at a mean follow-up of 33·3 months after a prespecified interim analysis showed that medical management alone was superior to the combination of medical management and interventional therapy in preventing symptomatic stroke or death. We aimed to study whether these differences persisted through 5-years' follow-up. METHODS: ARUBA was a non-blinded, randomised trial done at 39 clinical centres in nine countries. Adults (age ≥18 years) diagnosed with an unruptured brain arteriovenous malformation, who had never undergone interventional therapy, and were considered by participating clinical centres to be suitable for intervention to eradicate the lesion, were eligible for inclusion. Patients were randomly assigned (1:1) by a web-based data collection system, stratified by clinical centre in a random permuted block design with block sizes of two, four, and six, to medical management alone or with interventional therapy (neurosurgery, embolisation, or stereotactic radiotherapy, alone or in any combination, sequence, or number). Although patients and investigators at a given centre were not masked to treatment assignment, investigators at other centres and those in the clinical coordinating centre were not informed of assignment or outcomes at any of the centres. The primary outcome was time to death or symptomatic stroke confirmed by imaging, assessed by a neurologist at each centre not involved in the management of participants' care, and monitored by an independent committee using an adaptive approach with interim analyses. Enrolment began on April 4, 2007, and was halted on April 15, 2013, after which follow-up continued until July 15, 2015. All analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, NCT00389181. FINDINGS: Of 1740 patients screened, 226 were randomly assigned to medical management alone (n=110) or medical management plus interventional therapy (n=116). During a mean follow-up of 50·4 months (SD 22·9), the incidence of death or symptomatic stroke was lower with medical management alone (15 of 110, 3·39 per 100 patient-years) than with medical management with interventional therapy (41 of 116, 12·32 per 100 patient-years; hazard ratio 0·31, 95% CI 0·17 to 0·56). Two patients in the medical management group and four in the interventional therapy group (two attributed to intervention) died during follow-up. Adverse events were observed less often in patients allocated to medical management compared with interventional therapy (283 vs 369; 58·97 vs 78·73 per 100 patient-years; risk difference -19·76, 95% CI -30·33 to -9·19). INTERPRETATION: After extended follow-up, ARUBA showed that medical management alone remained superior to interventional therapy for the prevention of death or symptomatic stroke in patients with an unruptured brain arteriovenous malformation. The data concerning the disparity in outcomes should affect standard specialist practice and the information presented to patients. The even longer-term risks and differences between the two therapeutic approaches remains uncertain. FUNDING: National Institute of Neurological Disorders and Stroke for the randomisation phase and Vital Projects Fund for the follow-up phase.

Grades of brain arteriovenous malformations and risk of hemorrhage and death.

Objective: To assess the relationship of the grade of unruptured and untreated Brain Arteriovenous Malformations (AVMs), with the risk of subsequent stroke and death during follow-up. Methods: This prospective study was drawn from a cohort of adult patients with unruptured AVMs, who participated in the conservative treatment arm (medical management only for headache or seizures) of the randomized clinical trial of unruptured brain AVMs (ARUBA study). The grade of AVMs (Spetzler-Martin scale) was dichotomized into categories: AVMs of grades I and II were considered low grade; AVMs of grades III and IV were considered high grade. There were no grade V AVM patients in ARUBA. The primary outcome was symptomatic stroke (hemorrhagic or ischemic - documented by imaging) or death. Results: The conservative treatment group had 123 patients ("as treated" analysis). 71 (57.7%) had lesions characterized for this analysis as low-grade lesions and 52 (42.2%) as high grade. From the total of 10 (8.13%) primary outcomes, three occurred (4.22%) in low-grade AVMs and seven (13.46%) in high-grade AVMs (P = 0.0942). Interpretation: Statistical analysis of the cohort of patients with unruptured and untreated AVMs from ARUBA study showed that the graduation categories (Spetzler-Martin grades) were not associated with the outcome of subsequent stroke or death.