Heart failure, recurrent vascular events and death in patients with ischemic stroke-results of the MonDAFIS study.

Heart failure (HF) is associated with poor outcome after stroke, but data from large prospective trials are sparse.We assessed the impact of HF on clinical endpoints in patients hospitalized with acute ischemic stroke or transient ischemic attack (TIA) enrolled in the prospective, multicenter Systematic Monitoring for Detection of Atrial Fibrillation in Patients with Acute Ischemic Stroke (MonDAFIS) trial. HF was defined as left ventricular ejection fraction (LVEF) < 55% or a history of HF on admission. The composite of recurrent stroke, major bleeding, myocardial infarction, and all-cause death, and its components during the subsequent 24 months were assessed. We used estimated hazard ratios in confounder-adjusted models. Overall, 410/2562 (16.0%) stroke patients fulfilled the HF criteria (i.e. 381 [14.9%] with LVEF < 55% and 29 [1.9%] based on medical history). Patients with HF had more often diabetes, coronary and peripheral arterial disease and presented with more severe strokes on admission. HF at baseline correlated with myocardial infarction (HR 2.21; 95% CI 1.02-4.79), and all-cause death (HR 1.67; 95% CI 1.12-2.50), but not with major bleed (HR 1.93; 95% CI 0.73-5.06) or recurrent stroke/TIA (HR 1.08; 95% CI 0.75-1.57). The data were adjusted for age, stroke severity, cardiovascular risk factors, and randomization. Patients with ischemic stroke or TIA and comorbid HF have a higher risk of myocardial infarction and death compared with non-HF patients whereas the risk of recurrent stroke or major hemorrhage was similar. Trial registration number Clinicaltrials.gov NCT02204267.

Treatment-Relevant Findings in Transesophageal Echocardiography After Stroke: A Prospective Multicenter Cohort Study.

BACKGROUND AND PURPOSE: Cardiac ultrasound to identify sources of cardioembolism is part of the diagnostic workup of acute ischemic stroke. Recommendations on whether transesophageal echocardiography (TEE) should be performed in addition to transthoracic echocardiography (TTE) are controversial. We aimed to determine the incremental diagnostic yield of TEE in addition to TTE in patients with acute ischemic stroke with undetermined cause. METHODS: In a prospective, observational, pragmatic multicenter cohort study, patients with acute ischemic stroke or transient ischemic attack with undetermined cause before cardiac ultrasound were studied by TTE and TEE. The primary outcome was the rate of treatment-relevant findings in TTE and TEE as defined by a panel of experts based on current evidence. Further outcomes included the rate of changes in the assessment of stroke cause after TEE. RESULTS: Between July 1, 2017, and June 30, 2019, we enrolled 494 patients, of whom 492 (99.6%) received TTE and 454 (91.9%) received TEE. Mean age was 64.7 years, and 204 (41.3%) were women. TEE showed a higher rate of treatment-relevant findings than TTE (86 [18.9%] versus 64 [14.1%], P<0.001). TEE in addition to TTE resulted in 29 (6.4%) additional patients with treatment-relevant findings. Among 191 patients ≤60 years additional treatment-relevant findings by TEE were observed in 27 (14.1%) patients. Classification of stroke cause changed after TEE in 52 of 453 patients (11.5%), resulting in a significant difference in the distribution of stroke cause before and after TEE (P<0.001). CONCLUSIONS: In patients with undetermined cause of stroke, TEE yielded a higher number of treatment-relevant findings than TTE. TEE appears especially useful in younger patients with stroke, with treatment-relevant findings in one out of seven patients ≤60 years. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03411642.

Ten Years of Improving Acute Stroke Management in a Metropolitan Area: A Population-Based Quantification of Quality Indicators.

BACKGROUND AND PURPOSE: Rapid access to acute stroke treatment improves clinical outcomes in patients with ischemic stroke. We aimed to shorten the time to admission and to acute stroke treatment for patients with acute stroke in the Hamburg metropolitan area by collaborative multilevel measures involving all hospitals with stroke units, the Emergency Medical Services (EMS), and health-care authorities. METHODS: In 2007, an area-wide stroke care quality project was initiated. The project included mandatory admission of all stroke patients in Hamburg exclusively to hospitals with stroke units, harmonized acute treatment algorithms among all hospitals, repeated training of the EMS staff, a multimedia educational campaign, and a mandatory stroke care quality monitoring system based on structured data assessment and quality indicators for procedural measures. We analyzed data of all patients with acute stroke who received inhospital treatment in the city of Hamburg during the evaluation period from the quality assurance database data and evaluated trends of key quality indicators over time. RESULTS: From 2007 to 2016, a total of 83,395 patients with acute stroke were registered. During this period, the proportion of patients admitted within ≤3 h from symptom onset increased over time from 27.8% in 2007 to 35.2% in 2016 (p < 0.001). The proportion of patients who received rapid thrombolysis (within ≤30 min after admission) increased from 7.7 to 54.1% (p < 0.001). CONCLUSIONS: Collaborative stroke care quality projects are suitable and effective to improve acute stroke care.

Performance of implantable loop recorders. Role of R vector and detection algorithms.

INTRODUCTION: We evaluated the performance of implantable loop recorders (ILRs) with different detection algorithms and looked for artifacts and therapeutic consequences and their dependence on patient factors. METHODS AND RESULTS: 586 RevealLinq™ ILRs (first generation (NT): n = 335; second generation with TruRhythm™ (TR): n = 251) were implanted during 2014-2021 (syncope n = 206; embolic stroke of unknown source (ESUS) n = 380). Automatically detected EGM episodes (n = 18,650) were classified as correct or incorrect for asystole (AS), atrial fibrillation (AF) or tachycardia (TA). Incorrect episodes were caused by loss of signal (LO), noise (NO), extrasystole (ES) and T-wave oversensing (TWO). Left directed R axes, lower R-amplitudes and older age were related to artifacts. Results were separated by indication. In ESUS patients TR reduced total median artifact episodes: 0.6 (0-7) vs 0 (0-5) (p < 0.03) and median artifact examination time: 0.3 (0-3.5) vs 0 (0-2.5) (p = 0.03) per patient-year. This benefit is caused by significant reductions in total AS and ES-AS artifacts. The total positive predictive value (PPV) improved only in syncope patients (45 vs 71%, p = 0.002). Accordingly in syncope patients with TR more therapeutic consequences could be established (log rank 0.003). DISCUSSION: Patients R-axis and measured R-amplitudes during implantation predicted artifacts. This should be taken into account during ILR implantation. Total artifacts, AS artifacts and time spent for artifact analysis was reduced by the new TR detection algorithm in ESUS patients, whereas total artifacts remained unchanged in syncope patients despite reduction of AS artifacts. However TR had no effect on AF and TA episode detection and therefore has to be improved.

Rationale and design of an interventional study of cross-sectoral, coordinated treatment of stroke patients with patient-orientated outcome measurement (StroCare).

INTRODUCTION: Stroke has a long-term impact on functional status and quality of life in multiple health domains. A well-coordinated managed care program for stroke patients is crucial for ameliorating patients' health and cost-efficient use of resources. The aim of this study is the implementation and evaluation of an optimised cross-sectoral, coordinated and managed care program for stroke patients bridging secondary and tertiary care. METHODS: In this multi-center mixed method sequentially controlled intervention study, stroke patients with ischemic stroke (I63), transient ischemic attack and related syndromes (G45), or intracerebral haermorrhage (I64) will be invited to participate. For a 12-months period, 235 consecutive patients are expected to be enrolled and assigned standard of care treatment as an active control group. During the following 12 months, 235 consecutive patients will be enrolled and assigned to a post stroke intervention program. The StroCare intervention consists of repeated outpatient visits with specialized stroke teams, the implementation of a case manager, the use of an electronical tool for communication between acute care, rehabilitation facilities, and out-patient care, and the definition of individualized treatment targets. Patients will be followed up for 24 months. The primary outcome is health-related quality of life measured by the Patient-Reported Outcomes Measurement Information System 10-Question Short Form (PROMIS-10) at 12 months after the index event, i.e. stroke or TIA. For the qualitative survey of the implementation process, 21 patients in the intervention group will be interviewed after implementation of the interventions. In addition, 20 health care providers and staff members will be interviewed before and after implementation. Additionally, economic outcomes will be evaluated after 6 and 12 months. PERSPECTIVE: The study will not only provide information about the tested intervention but is likely to be helpful for clinicians, suppliers of reimbursement, and researchers in implementing and evaluating complex interventions in stroke care in general. With this program, the health care system will have a reference model at its disposal for transfer to other regions and settings. TRIAL REGISTRATION: The trial is registered at ClinicalTrials.gov ( NCT04159324 ). Approval of the local ethics committee (Ethik-Kommission der Ärztekammer Hamburg, Niedersachsen, Schleswig-Holstein) has been obtained.

Bedsided Transcranial Sonographic Monitoring for Expansion and Progression of Subdural Hematoma Compared to Computed Tomography.

INTRODUCTION: Transcranial high-resolution ultrasonography reliably allows diagnosis and monitoring of intracerebral hemorrhage in adults. Sonographic monitoring of subdural hematoma (SDH) has not been evaluated in adults so far. This study investigates the reliability of transcranial gray-scale sonography (TGS) in monitoring acute and chronic SDH in adults. METHODS: TGS was performed in 47 consecutive patients with either acute or chronic SDH confirmed by cerebral CT. Four patients were excluded due to insufficient bone window. After identification of SDH in TGS extent was measured and correlated with extent of SDH on cerebral computer tomography (CCT). If possible measurement was performed at least on 2 days to evaluate the possibility to monitor SDH with TGS. RESULTS: In 43 patients with SDH, 76 examinations were performed with 2 examinations in 23 patients and 3 examinations in 10 patients. Overall extent of SDH correlated significantly between TGS and CCT (r = 0.962). Accordingly correlation was high during each single examination time point. In patients in need for surgical evacuation sonographic measurement yielded a sensitivity of 90.9% and specificity of 93.8% in predicting surgical evacuation (p < 0.001). DISCUSSION: Imaging of SDH with TGS is possible in patients with SDH and extent of SDH correlates significantly between TGS and CCT during initial as well as during follow-up examination. Thus monitoring of SDH with TGS at patients' bedside is possible.

Real-world experience of treatment decision-making in carotid stenosis in a neurovascular board.

OBJECTIVE: To describe our experience with consensus-based decision-making for treatment of internal carotid artery (ICA) stenosis by neurologists, interventional neuroradiologists, vascular surgeons, and neurosurgeons in a multidisciplinary neurovascular board and to study adherence to treatment recommendations in the context of uncertainty with respect to the best treatment option. METHODS: We established a multidisciplinary neurovascular board meeting twice a week with structured documentation of consensus decisions. Over a time period of 53 months, 614 cases with ICA stenosis were discussed, with 285 (46%) symptomatic and 279 (45%) asymptomatic cases. RESULTS: Recommendation for symptomatic ICA stenosis was revascularization in 76%, medical management alone in 8%, and further diagnostics in 16%. For asymptomatic ICA stenosis, recommendation was randomization in a clinical trial in 29%, revascularization in 27%, medical management alone in 23%, and further diagnostics in 22%. Treatment recommendations were followed in 94% of symptomatic ICA stenosis and 69% of asymptomatic ICA stenosis. Patients in whom carotid artery stenting was recommended for revascularization were younger and showed a higher rate of severe (≥70%) ICA stenosis. CONCLUSIONS: Interdisciplinary board decisions are a helpful and transparent tool to assure adherence to guideline recommendations, and to provide consensus-based individualized treatment strategies in clinical practice in the absence of unequivocal evidence.

Subjective and objective knowledge and decisional role preferences in cerebrovascular patients compared to controls.

BACKGROUND: Risk knowledge and active role preferences are important for patient involvement in treatment decision-making and adherence. Although knowledge about stroke warning signs and risk factors has received considerable attention, objective knowledge on secondary prevention and further self-esteem subjective knowledge have rarely been studied. The aim of our study was to investigate knowledge and treatment decisional role preferences in cerebrovascular patients compared to controls. METHODS: We performed a survey on subjective and objective stroke risk knowledge and autonomy preferences in cerebrovascular patients from our stroke outpatient clinic (n=262) and from pedestrians on the street taken as controls during a "World Stroke Day" (n=274). The questionnaire includes measures for knowledge and decisional role preferences from previously published questionnaires and newly developed measures, for example, subjective knowledge, revealed on a visual analog scale. RESULTS: The overall stroke knowledge was low to moderate, with no differences between patients and controls. Knowledge about secondary prevention was particularly low. Only 10%-15% of participants correctly estimated the stroke absolute risk reduction potential of aspirin. The medical data interpretation competence was moderate in both groups. Age and basic mathematical and statistical understanding (numeracy) were the only independent predictors of objective stroke knowledge, whereas previous stroke had no impact on stroke knowledge. However, patients were thought to be better informed than controls. Approximately 60% of both patients and controls claimed to prefer a shared decision-making approach in treatment decisions. CONCLUSION: The level of stroke risk knowledge in patients with cerebrovascular diseases was as low as in randomly selected pedestrians, although patients felt better informed. Both groups preferred involvement in treatment decision-making. We conclude that educational concepts for increasing awareness of knowledge gaps as well as for stroke risk and for prevention strategies are needed.

Elective treatment of intracranial stenosis with the balloon-expandable Pharos Vitesse stent: 30-day stroke rate and complications.

BACKGROUND AND PURPOSE: Analysis of procedural results and 30-day outcome after intracranial angioplasty and stenting (ICAS) with the balloon-expandable Pharos Vitesse stent system in carefully selected high-risk patients in two high-volume neurovascular centers. MATERIALS AND METHODS: 92 patients scheduled for elective ICAS using Pharos Vitesse between August, 2008 and August, 2011 were included. All patients showed high-grade intracranial stenosis and recurrent ischemic events despite best medical treatment at that time. The stroke rates and complications were divided into procedural and 30-day short-term events. RESULTS: Successful stent placement was achieved in all but one patient. Ischemic procedural complications occurred in three subjects. 30-Day complications and strokes were seen in four patients: two minor ischemic strokes, one fatal hemorrhage and one non-stroke-related death. Overall, strokes occurred in 6 out of 92 patients (6.5%, 95% CI 3.0% to 13.5%). The total stroke and death rate was 7.6% (95% CI 3.7% to 14.9%). No significant correlation with previously reported risk factors could be found, although a higher rate of ischemic strokes (four out of five) in the posterior circulation was recorded. CONCLUSIONS: In patients with intracranial stenosis who experience recurrent ischemic events despite best medical treatment, ICAS, using the balloon-expandable Pharos Vitesse stent, may still be considered as an individual treatment option in high-volume neurovascular centers.

The extent of perfusion deficit does not relate to the visibility of acute ischemic lesions on fluid-attenuated inversion recovery imaging.

OBJECTIVES: Fluid-attenuated inversion recovery imaging (FLAIR) has been suggested as a surrogate marker of lesion age in acute ischemic stroke. In a subgroup analysis, we evaluated whether the extent of perfusion deficit influences FLAIR lesion visibility and thus plays a role as a confounding variable in the interpretation of FLAIR images. METHODS: A subgroup of patients from a previous study evaluating the use of FLAIR imaging as a surrogate marker of lesion age within the first 6 hours of ischemic stroke were examined to determine the influence of the amount of perfusion deficit on FLAIR lesion visibility. RESULTS: N = 48 patients were included into the analysis. In positive and negative FLAIR lesion cases the extent of perfusion deficits did not differ significantly (150 mL vs. 197 mL, P = .730) nor influenced FLAIR visibility independently. In contrast, diffusion weighted imaging (DWI) lesion volumes were larger (34 mL vs. 14 mL, P = .008) and time from symptom onset longer (180 vs. 120 minute, P = .071) in FLAIR-positive cases. CONCLUSION: Visibility of FLAIR lesions in acute stroke imaging is influenced by lesion size and time from symptom onset to MRI, but not by the amount of perfusion deficit calculated by time-to-peak (TTP) measurements.

Outcome of MRI-based intravenous thrombolysis in carotid-T occlusion.

Low recanalization rates and poor clinical outcome have been reported after intravenous thrombolysis (IV-tPA) in carotid-T occlusion (CTO). We studied clinical outcome and imaging findings of MRI-based intravenous thrombolysis in CTO. Data of patients with acute ischemic stroke and CTO treated with IV-tPA within 6 h of symptom onset based on MRI criteria were retrospectively analyzed. Vessel occlusion was defined based on MR angiography. Acute diffusion and perfusion lesion volumes and final infarct volumes after 3-7 days were delineated. The National Institutes of Health Stroke Scale (NIHSS) was used to assess the neurological deficit on admission. Recanalization was evaluated after 24 h. Clinical outcome was assessed using the modified Rankin Scale (mRS) after 90 days. Clinical and imaging data were compared to patients with middle cerebral artery main stem occlusion (MCAO). A total of 20 patients with CTO and 51 patients with MCAO were studied. Onset to treatment time, NIHSS on admission, initial diffusion and perfusion lesion volumes, and recanalization rates after 24 h were similar between groups. Final infarct volume was larger for CTO (82 vs. 30 ml, p = 0.006). Although overall outcome was not significantly different between groups (p = 0.251), independent outcome (mRS 0-2) tended to be less frequent in CTO (17 vs. 39 %), while poor outcome (mRS 4-6) appeared more common (72 vs. 43 %). The proportion of patients with good clinical outcome after intravenous thrombolysis in CTO is small. Moreover, final infarct volume is larger and clinical outcome appears to be worse compared to MCAO.

Predictors of periprocedural brain lesions associated with carotid stenting.

BACKGROUND: Carotid stenting carries a risk of periprocedural stroke. We aimed at determining predictors of cerebral ischemic events associated with stenting for symptomatic carotid stenosis. METHODS: 127 patients who had been studied by diffusion-weighted MR imaging (DWI) before and on the day after carotid stenting were included. Six clinical variables and 5 variables characterizing the target carotid artery and aortic atherosclerosis were analyzed as potential risk factors for new ipsilateral DWI lesions after stenting. RESULTS: Among all variables assessed, only age, length of stenosis and carotid intima-media thickness (IMT) significantly modified the risk of new lesions after stenting. Age ≥68 years, stenosis ≥15 mm and IMT ≥1.3 mm were identified as the best thresholds to predict new lesions. In the subgroup of patients ≥68 years with carotid stenosis ≥15 mm in length and IMT ≥1.3 mm, the risk of new lesions was markedly higher than in patients to whom no more than two of these factors applied (odds ratio 7.250, 95% CI 1.612-34.513, p = 0.005). The use of this simple predictive model correctly identified patients who had new lesions after stenting with high specificity (0.96) and a negative predictive value (0.83), while the positive predictive value was moderate (0.60) and sensitivity was low (0.23). CONCLUSIONS: The risk of stenting for symptomatic carotid stenosis may vary with clinical and morphological patient characteristics. Further research is needed to validate these results and to evaluate the safety of stenting versus endarterectomy in specific patient subgroups.

DWI-FLAIR mismatch for the identification of patients with acute ischaemic stroke within 4·5 h of symptom onset (PRE-FLAIR): a multicentre observational study.

BACKGROUND: Many patients with stroke are precluded from thrombolysis treatment because the time from onset of their symptoms is unknown. We aimed to test whether a mismatch in visibility of an acute ischaemic lesion between diffusion-weighted MRI (DWI) and fluid-attenuated inversion recovery (FLAIR) MRI (DWI-FLAIR mismatch) can be used to detect patients within the recommended time window for thrombolysis. METHODS: In this multicentre observational study, we analysed clinical and MRI data from patients presenting between Jan 1, 2001, and May 31, 2009, with acute stroke for whom DWI and FLAIR were done within 12 h of observed symptom onset. Two neurologists masked to clinical data judged the visibility of acute ischaemic lesions on DWI and FLAIR imaging, and DWI-FLAIR mismatch was diagnosed by consensus. We calculated predictive values of DWI-FLAIR mismatch for the identification of patients with symptom onset within 4·5 h and within 6 h and did multivariate regression analysis to identify potential confounding covariates. This study is registered with ClinicalTrials.gov, number NCT01021319. FINDINGS: The final analysis included 543 patients. Mean age was 66·0 years (95% CI 64·7-67·3) and median National Institutes of Health Stroke Scale score was 8 (IQR 4-15). Acute ischaemic lesions were identified on DWI in 516 patients (95%) and on FLAIR in 271 patients (50%). Interobserver agreement for acute ischaemic lesion visibility on FLAIR imaging was moderate (κ=0·569, 95% CI 0·504-0·634). DWI-FLAIR mismatch identified patients within 4·5 h of symptom onset with 62% (95% CI 57-67) sensitivity, 78% (72-84) specificity, 83% (79-88) positive predictive value, and 54% (48-60) negative predictive value. Multivariate regression analysis identified a longer time to MRI (p<0·0001), a lower age (p=0·0009), and a larger DWI lesion volume (p=0·0226) as independent predictors of lesion visibility on FLAIR imaging. INTERPRETATION: Patients with an acute ischaemic lesion detected with DWI but not with FLAIR imaging are likely to be within a time window for which thrombolysis is safe and effective. These findings lend support to the use of DWI-FLAIR mismatch for selection of patients in a future randomised trial of thrombolysis in patients with unknown time of symptom onset. FUNDING: Else Kröner-Fresenius-Stiftung, National Institutes of Health.

Carotid plaque surface irregularity predicts cerebral embolism during carotid artery stenting.

BACKGROUND AND PURPOSE: Carotid artery stenting (CAS) is associated with the risk of periprocedural embolic events. The procedural risk may vary with plaque characteristics. We aimed at determining the impact of carotid plaque surface irregularity on the risk of cerebral embolism during CAS. METHODS: Solid microembolic signals (MES) during CAS for symptomatic carotid stenosis were assessed by means of dual-frequency transcranial Doppler ultrasound. Study endpoint was the number of solid MES during CAS in 12 patients with irregular carotid stenosis compared to 12 matched patients with smooth carotid stenosis. RESULTS: A total of 438 solid MES were detected. The cumulative number of solid MES was 329 in patients with irregular plaques and 109 in those with smooth plaques. The proportion of subjects in whom solid MES were detected was higher in the irregular plaque group (11/12) than in the smooth plaque group (5/12) (p = 0.030). The numbers of solid MES per CAS procedure and per hour of CAS procedure were both higher in patients with irregular plaques than in those with smooth plaques (p = 0.008 and 0.015, respectively). CONCLUSIONS: Carotid plaque surface irregularity predicts solid cerebral embolism during stenting of symptomatic carotid artery stenosis.

Pretreatment diffusion-weighted imaging lesion volume predicts favorable outcome after intravenous thrombolysis with tissue-type plasminogen activator in acute ischemic stroke.

BACKGROUND AND PURPOSE: Stroke magnetic resonance imaging with perfusion and diffusion weighting has shown its potential to select patients likely to benefit from intravenous thrombolysis with tissue-type plasminogen activator (IV-tPA). We aimed to determine the predictors of favorable outcome in magnetic resonance imaging-selected, acute stroke patients treated with IV-tPA. METHODS: We analyzed the data of acute ischemic stroke patients from a prospective, multicenter, observational study of magnetic resonance imaging-based IV-tPA treatment initiated ≤6 hours from symptom onset. Neurologic deficit on admission was assessed by the National Institutes of Health Stroke Scale. Clinical outcome was assessed after 90 days according to the modified Rankin Scale. Favorable outcome was defined as a modified Rankin Scale score of 0 to 1. Patients were compared regarding baseline parameters. Multivariate regression analysis was used to identify predictors of favorable outcome. RESULTS: Of 174 patients, 83 (48%) reached a favorable outcome. They were younger (median age, 62 versus 67 years; P=0.001), had a lower National Institutes of Health Stroke Scale score on admission (median, 11 versus 15; P<0.001), and had smaller diffusion-weighted imaging lesions (median, 12.9 versus 20 mL; P=0.001). Perfusion-weighted imaging lesion volumes and onset-to-treatment time were comparable between the groups. Age (P=0.017), National Institutes of Health Stroke Scale score on admission (P<0.001), and diffusion-weighted imaging lesion volume (P=0.047) were identified as independent predictors of favorable outcome. CONCLUSIONS: A lower age, lower National Institutes of Health Stroke Scale score on admission, and smaller pretreatment diffusion-weighted imaging lesion volume were found to be associated with a favorable outcome after treatment with IV-tPA. Pretreatment perfusion lesion volume and onset-to-treatment time were not associated with outcome when patients were selected for IV-tPA by magnetic resonance imaging within 6 hours of symptom onset.

Dynamics of regional distribution of ischemic lesions in middle cerebral artery trunk occlusion relates to collateral circulation.

We describe the regional distribution of acute perfusion, diffusion, and final infarct lesions in middle cerebral artery (MCA) trunk occlusion. A total of 31 patients with acute ischemic stroke and MCA trunk occlusion were studied by multiparametric magnetic resonance imaging. Probabilistic maps of lesion distribution were generated. The probability of initial and final infarcts was highest in the central MCA region with decreasing probability toward the periphery where the probability of the tissue at risk of infarction to be saved was highest. The probability of brain regions being involved in acute diffusion lesions and evolving into or escaping from the final infarct relates to the anatomy of arterial blood supply.

Older age and greater carotid intima-media thickness predict ischemic events associated with carotid-artery stenting.

BACKGROUND: Carotid-artery stenting (CAS) may be complicated by stroke. We aimed to determine predictors of procedure-related ischemic events. METHODS: We analyzed new ischemic lesions in diffusion-weighted MRI (DWI) after CAS in 147 patients with symptomatic high-grade carotid stenosis. Nine covariates were assessed as potential risk factors for new lesions in DWI: age, gender, hypertension, diabetes, dyslipidemia, smoking status, severity of stenosis, side of intervention and carotid intima-media thickness (IMT). RESULTS: From the nine covariates assessed, only age and IMT were independently associated with new DWI lesions. An age of 68 years and an IMT of 1.5 mm gave the best separation between high- and low-risk populations. The subgroup of patients <68 years who had an IMT ≤1.5 mm had the lowest rate of new DWI lesions (11.3%). This rate was greater in patients ≥68 years (30.0%; odds ratio, OR, 3.4; 95% confidence interval, CI, 1.1-10.8) and in patients with an IMT >1.5 mm (36.4%; OR 4.5; 95% CI 1.2-17.0) and was particularly high in patients aged ≥68 years with IMT >1.5 mm (69.6%; OR 18.0; 95% CI 4.8-71.9). CONCLUSIONS: Older age and greater IMT are independently associated with the risk of CAS-related ischemic events. This risk is particularly high in those patients in whom older age and greater IMT coincide.

AXIS: a trial of intravenous granulocyte colony-stimulating factor in acute ischemic stroke.

BACKGROUND AND PURPOSE: Granulocyte colony-stimulating factor (G-CSF) is a promising stroke drug candidate. The present phase IIa study assessed safety and tolerability over a broad dose range of G-CSF doses in acute ischemic stroke patients and explored outcome data. METHODS: Four intravenous dose regimens (total cumulative doses of 30-180 µg/kg over the course of 3 days) of G-CSF were tested in 44 patients in a national, multicenter, randomized, placebo-controlled dose escalation study (NCT00132470; www.clinicaltrial.gov). Main inclusion criteria were a 12-hour time window after stroke onset, infarct localization to the middle cerebral artery territory, a baseline National Institutes of Health Stroke Scale range of 4 to 22, and presence of diffusion-weighted imaging/perfusion-weighted imaging mismatch. RESULTS: Concerning the primary safety end points, we observed no increase of thromboembolic events in the active treatment groups, and no increase in related serious adverse events. G-CSF led to expected increases in neutrophils and monocytes that resolved rapidly after end of treatment. We observed a clinically insignificant drug-related decrease of platelets. As expected from the low number of patients, we did not observe significant differences in clinical outcome in treatment vs. placebo. In exploratory analyses, we observed an interesting dose-dependent beneficial effect of treatment in patients with DWI lesions > 14-17 cm³. CONCLUSIONS: We conclude that G-CSF was well-tolerated even at high dosages in patients with acute ischemic stroke, and that a substantial increase in leukocytes appears not problematic in stroke patients. In addition, exploratory analyses suggest treatment effects in patients with larger baseline diffusion-weighted imaging lesions. The obtained data provide the basis for a second trial aimed to demonstrate safety and efficacy of G-CSF on clinical end points.