The relationship of pro-inflammatory markers to vascular endothelial function after acute stroke.

Purpose/Aim: Data from chronic stroke studies have reported reduced blood flow and vascular endothelial function in the stroke-affected limb. It is unclear whether these differences are present early after stroke. First, we investigated whether vascular endothelial function in the stroke-affected limb would be different from healthy adults. Second, we examined whether between-limb differences in vascular endothelial function existed in the stroke-affected arm compared to the non-affected arm. Last, we tested whether reduced vascular endothelial function was related to pro-inflammatory markers that are present early after stroke. MATERIALS AND METHODS: Vascular endothelial function was assessed by flow-mediated dilation (FMD) in the brachial artery within 72 h post-stroke. All participants withheld medications from midnight until after the procedure. Ultrasound scans and blood draws for pro-inflammatory markers occurred on the same day between 7:30 am and 9:00 am. RESULTS: People with acute stroke had significantly lower FMD (4.2% ± 4.6%) than control participants (8.5% ± 5.2%, p = 0.037). Stroke participants had between-limb differences in FMD (4.2% ± 4.6% stroke-affected vs. 5.3% ± 4.4% non-affected, p = 0.02), whereas, the control participants did not. Of the pro-inflammatory markers, only vascular cell adhesion molecule-1(VCAM-1) had a significant relationship to FMD (stroke-affected limb, r = -0.62, p = 0.03; non-affected limb, r = -0.75, p = 0.005), but not tumor necrosis factor alpha nor interleukin-6. CONCLUSIONS: Vascular endothelial function is reduced starting in the early stage of stroke recovery. People with higher levels of VCAM-1 had a lower FMD response.

Predictors for atrial fibrillation detection after cryptogenic stroke: Results from CRYSTAL AF.

OBJECTIVE: We assessed predictors of atrial fibrillation (AF) in cryptogenic stroke (CS) or transient ischemic attack (TIA) patients who received an insertable cardiac monitor (ICM). METHODS: We studied patients with CS/TIA who were randomized to ICM within the CRYSTAL AF study. We assessed whether age, sex, race, body mass index, type and severity of index ischemic event, CHADS2 score, PR interval, and presence of diabetes, hypertension, congestive heart failure, or patent foramen ovale and premature atrial contractions predicted AF development within the initial 12 and 36 months of follow-up using Cox proportional hazards models. RESULTS: Among 221 patients randomized to ICM (age 61.6 ± 11.4 years, 64% male), AF episodes were detected in 29 patients within 12 months and 42 patients at 36 months. Significant univariate predictors of AF at 12 months included age (hazard ratio [HR] per decade 2.0 [95% confidence interval 1.4-2.8], p = 0.002), CHADS2 score (HR 1.9 per one point [1.3-2.8], p = 0.008), PR interval (HR 1.3 per 10 milliseconds [1.2-1.4], p < 0.0001), premature atrial contractions (HR 3.9 for >123 vs 0 [1.3-12.0], p = 0.009 across quartiles), and diabetes (HR 2.3 [1.0-5.2], p < 0.05). In multivariate analysis, age (HR per decade 1.9 [1.3-2.8], p = 0.0009) and PR interval (HR 1.3 [1.2-1.4], p < 0.0001) remained significant and together yielded an area under the receiver operating characteristic curve of 0.78 (0.70-0.85). The same predictors were found at 36 months. CONCLUSION: Increasing age and a prolonged PR interval at enrollment were independently associated with an increased AF incidence in CS patients. However, they offered only moderate predictive ability in determining which CS patients had AF detected by the ICM.

Infarct Topography and Detection of Atrial Fibrillation in Cryptogenic Stroke: Results from CRYSTAL AF.

BACKGROUND: Insertable cardiac monitors (ICM) have been shown to detect atrial fibrillation (AF) at a higher rate than routine monitoring methods in patients with cryptogenic stroke (CS). However, it is unknown whether there are topographic patterns of brain infarction in patients with CS that are particularly associated with underlying AF. If such patterns exist, these could be used to help decide whether or not CS patients would benefit from long-term monitoring with an ICM. METHODS: In this retrospective analysis, a neuro-radiologist blinded to clinical details reviewed brain images from 212 patients with CS who were enrolled in the ICM arm of the CRYptogenic STroke And underLying AF (CRYSTAL AF) trial. Kaplan-Meier estimates were used to describe rates of AF detection at 12 months in patients with and without pre-specified imaging characteristics. Hazard ratios (HRs), 95% confidence intervals (CIs), and p values were calculated using Cox regression. RESULTS: We did not find any pattern of acute brain infarction that was significantly associated with AF detection after CS. However, the presence of chronic brain infarctions (15.8 vs. 7.0%, HR 2.84, 95% CI 1.13-7.15, p = 0.02) or leukoaraiosis (18.2 vs. 7.9%, HR 2.94, 95% CI 1.28-6.71, p < 0.01) was associated with AF detection. There was a borderline significant association of AF detection with the presence of chronic territorial (defined as within the territory of a first or second degree branch of the circle of Willis) infarcts (20.9 vs. 10.0%, HR 2.37, 95% CI 0.98-5.72, p = 0.05). CONCLUSIONS: We found no evidence for an association between brain infarction pattern and AF detection using an ICM in patients with CS, although patients with coexisting chronic, as well as acute, brain infarcts had a higher rate of AF detection. Acute brain infarction topography does not reliably predict or exclude detection of underlying AF in patients with CS and should not be used to select patients for ICM after cryptogenic stroke.

A Comparison of Atrial Fibrillation Monitoring Strategies After Cryptogenic Stroke (from the Cryptogenic Stroke and Underlying AF Trial).

Ischemic stroke cause remains undetermined in 30% of cases, leading to a diagnosis of cryptogenic stroke. Paroxysmal atrial fibrillation (AF) is a major cause of ischemic stroke but may go undetected with short periods of ECG monitoring. The Cryptogenic Stroke and Underlying Atrial Fibrillation trial (CRYSTAL AF) demonstrated that long-term electrocardiographic monitoring with insertable cardiac monitors (ICM) is superior to conventional follow-up in detecting AF in the population with cryptogenic stroke. We evaluated the sensitivity and negative predictive value (NPV) of various external monitoring techniques within a cryptogenic stroke cohort. Simulated intermittent monitoring strategies were compared to continuous rhythm monitoring in 168 ICM patients of the CRYSTAL AF trial. Short-term monitoring included a single 24-hour, 48-hour, and 7-day Holter and 21-day and 30-day event recorders. Periodic monitoring consisted of quarterly monitoring through 24-hour, 48-hour, and 7-day Holters and monthly 24-hour Holters. For a single monitoring period, the sensitivity for AF diagnosis was lowest with a 24-hour Holter (1.3%) and highest with a 30-day event recorder (22.8%). The NPV ranged from 82.3% to 85.6% for all single external monitoring strategies. Quarterly monitoring with 24-hour Holters had a sensitivity of 3.1%, whereas quarterly 7-day monitors increased the sensitivity to 20.8%. The NPVs for repetitive periodic monitoring strategies were similar at 82.6% to 85.3%. Long-term continuous monitoring was superior in detecting AF compared to all intermittent monitoring strategies evaluated (p <0.001). Long-term continuous electrocardiographic monitoring with ICMs is significantly more effective than any of the simulated intermittent monitoring strategies for identifying AF in patients with previous cryptogenic stroke.

Use of Accelerometers to Examine Sedentary Time on an Acute Stroke Unit.

BACKGROUND AND PURPOSE: Observational studies demonstrate low levels of physical activity during inpatient stroke rehabilitation. There are no prior studies that have objectively measured sedentary time on the acute stroke unit and whether sedentary time is related to functional outcomes. The purpose of this study was to characterize sedentary time after acute stroke and determine whether there is a relationship to functional performance at discharge. METHODS: Thirty-two individuals (18 men; 56.5 ± 12.7 years) with acute stroke were enrolled within 48 hours of hospital admission. An accelerometer was placed on the stroke-affected ankle to measure 24-hour activity and was worn for 4 days or until discharge from the hospital. Performance of activities of daily living, walking endurance, and functional mobility were assessed using the Physical Performance Test, Six-Minute Walk Test, and Timed Up and Go, respectively. RESULTS: Mean percent time spent sedentary was 93.9 ± 4.1% and percent time in light activity was 5.1 ± 2.4%. When controlling for baseline performance, the mean time spent sedentary per day was significantly related to Physical Performance Test performance at discharge (r = -0.37; P = .05), but not the Six-Minute Walk Test or Timed Up and Go. DISCUSSION AND CONCLUSIONS: Patients with acute stroke were sedentary most of their hospital stay. To minimize the potential negative effects of inactivity, our data suggest that there should be greater emphasis on increasing physical activity during the hospital stay.Video Abstract Available for more insights from the authors (Supplemental Digital Content 1, http://links.lww.com/JNPT/A101).

Predictors and clinical relevance of hemorrhagic transformation after endovascular therapy for anterior circulation large vessel occlusion strokes: a multicenter retrospective analysis of 1122 patients.

BACKGROUND AND PURPOSE: Endovascular techniques are frequently employed to treat large artery occlusion in acute ischemic stroke (AIS). We sought to determine the predictors and clinical impact of intracranial hemorrhage (ICH) after endovascular therapy. METHODS: Retrospective analysis of consecutive patients presenting to 13 high volume stroke centers with AIS due to proximal occlusion in the anterior circulation who underwent endovascular treatment within 8 h from symptom onset. Logistic regression was performed to determine the variables associated with ICH, hemorrhagic infarction (HI), and parenchymal hematomas (PHs), as well as 90 day poor outcome (modified Rankin Scale score ≥3) and mortality. RESULTS: There were a total of 363 ICHs (overall rate 32.3%; HI=267, 24%; PH=96, 8.5%) among the 1122 study patients (mean age 67±15 years; median National Institutes of Health Stroke Scale score 17 (IQR 13-20)). Independent predictors for HI included diabetes mellitus (OR 2.27, 95% CI (1.58 to 3.26), p<0.0001), preprocedure IV tissue plasminogen activator (tPA) (1.43 (1.03 to 2.08), p<0.037), Merci thrombectomy (1.47 (1.02 to 2.12), p<0.032), and longer time to puncture (1.001 (1.00 to 1.002), p<0.026). Patients with atrial fibrillation (1.61 (1.01 to 2.55), p<0.045) had a higher risk of PH while the use of IA tPA (0.57 (0.35 to 0.90), p<0.008) was associated with lower chances of PH. Both the presence of HI (2.23 (1.53 to 3.25), p<0.0001) and PH (6.24 (3.06 to 12.75), p<0.0001) were associated with poor functional outcomes; however, only PH was associated with higher mortality (3.53 (2.19 to 5.68), p<0.0001). CONCLUSIONS: Greater understanding about the predictors and consequences of ICH post endovascular stroke therapy is essential to improve risk assessment, patient selection/clinical outcomes, and early prognostication. Our data suggest that patients with atrial fibrillation are particularly prone to severe ICH and question the 'benign' nature of HI suggested by earlier studies.

Analysis of the costs and payments of a coordinated stroke center and regional stroke network.

BACKGROUND AND PURPOSE: An earlier study demonstrated significantly improved access, treatment, and outcomes after the implementation of a progressive, comprehensive stroke program at a tertiary care community hospital, Saint Luke's Neuroscience Institute (SLNI). This study evaluated the costs associated with implementing such a program. METHODS: Retrospective analysis of total hospital costs and payments for treating patients with ischemic stroke at SLNI (n=1570) as program enhancement evolved over time (2005, 2007, and 2010) and compared with published national estimates. Analyses were stratified by patient demographic characteristics, patient outcomes, treatments, time, and comorbidities. RESULTS: Controlling for inflation, there was no difference in SLNI total costs between 2005 and either 2007 or 2010, suggesting that while SLNI provided an increased level of services, any additional expenditures were offset by efficiencies. SLNI total costs were slightly lower than published benchmarks. Consistent with previous stroke care cost estimates, the median overall differential between total hospital costs and payments for all ischemic stroke cases was negative. CONCLUSIONS: SLNI total costs remained consistent over time and were slightly lower than previously published estimates, suggesting that a focused, streamlined stroke program can be implemented without a significant economic impact. This finding further demonstrates that providing comprehensive stroke care with improved access and treatment may be financially feasible for other hospitals.

Analysis of a coordinated stroke center and regional stroke network on access to acute therapy and clinical outcomes.

BACKGROUND AND PURPOSE: Compare access and outcomes in a tertiary care community hospital (Saint Luke's Neuroscience Institute) and its stroke network to hospitals in 3 national databases. METHODS: Retrospective analysis of ischemic stroke patients (2005, 2007, 2010) in Saint Luke's (n=1576), Get With The Guidelines-Stroke (n=423 809), Premier (n=91 598), and Merci Registry (n=966). Study measures were use of computed tomography scans and tissue plasminogen activator (tPA), symptomatic intracranial hemorrhage, discharge disposition, discharge National Institutes of Health Stroke Scale scores, and 90-day modified Rankin Scores. RESULTS: Saint Luke's increased access to care with higher tPA use than other hospitals (17.2% received intravenous tPA therapy compared with 5.8% at Get With The Guidelines-Stroke hospitals, P<0.001; 22.1% of Saint Luke's patients received tPA by any route compared with 3.5% of Premier patients, P<0.001). Use of intravenous tPA within 4.5 hours of onset was associated with more discharges to home (odds ratio, 2.123; 95% confidence interval, 1.394-3.246) and improved National Institutes of Health Stroke Scale scores (P=0.001). Saint Luke's patients also were more likely than those in other hospitals to receive computed tomography scans (99.4% vs 58.6% at Premier hospitals). Embolectomy at Saint Luke's was associated with better outcomes than peer hospitals, and treatment at Saint Luke's was independently associated with more discharges to home (odds ratio, 3.92; 95% confidence interval, 1.84-8.32). In 2010, symptomatic intracranial hemorrhages after tPA therapy was similar for Saint Luke's patients and Premier patients (2.2% vs 1.5%; P=0.590). CONCLUSIONS: Regionally coordinated stroke programs can substantially improve access and patient outcomes.

Hemorrhagic stroke: aneurysmal subarachnoid hemorrhage.

Non-traumatic subarachnoid hemorrhage (SAH) represents approximately 5-6% of all strokes. Morbidity and mortality rates remain high, but accurate diagnosis using clinical assessment and neuroimaging, critical care management, and early treatment using either surgical or interventional techniques have improved overall outcomes. This, the fifth in a Missouri Medicine series on stroke, summarizes the clinical and imaging aspects of making the diagnosis of SAH, critical care management of the patient, treatment options, and factors important in prognosis.

Hemorrhagic stroke: intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is a devastating event, carrying a very high morbidity and mortality rate. Hypertension and age-related amyloid angiopathy are the strongest risk factors for ICH, but smoking, anticoagulation with warfarin, excessive alcohol intake and cocaine also increase risk. This, the fourth in a Missouri Medicine series on stroke summarizes the clinical and imaging aspects of making the diagnosis of ICH. Current medical and surgical therapies are discussed as well as predictors of outcome and recommendations for secondary prevention.

Prediction of adverse outcomes by blood glucose level after endovascular therapy for acute ischemic stroke.

OBJECT: The authors evaluated the prognostic significance of blood glucose level at admission (BGA) and change in blood glucose at 48 hours from the baseline value (CG48) in nondiabetic and diabetic patients before and after endovascular therapy for acute ischemic stroke (AIS). METHODS: The BGA and CG48 data were analyzed in 614 patients with AIS who received endovascular therapy at 7 US centers between 2006 and 2009. Data reviewed included demographics, stroke risk factors, diabetic status, National Institutes of Health Stroke Scale (NIHSS) score at presentation, recanalization grade, intracranial hemorrhage (ICH) rate, and 90-day outcomes (mortality rate and modified Rankin Scale score of 3-6 [defined as poor outcome]). Variables with p values < 0.2 in univariate analysis were included in a binary logistic regression model for independent predictors of 90-day outcomes. RESULTS: The mean patient age was 67.3 years, the median NIHSS score was 16, and 27% of patients had diabetes. In nondiabetic patients, BGA ≥ 116 mg/dl (≥ 6.4 mmol/L) and failure of glucose level to drop > 30 mg/dl (> 1.7 mmol/L) from the admission value were both significant predictors of 90-day poor outcome and death (p < 0.001). In patients with diabetes, BGA ≥ 116 mg/dl (≥ 6.4 mmol/L) was an independent predictor of poor outcome (p = 0.001). The CG48 was not a predictor of outcome in diabetic patients. A simplified 6-point scale including BGA, Thrombolysis in Myocardial Infarction (TIMI) Grade 2-3 Reperfusion, Age, presentation NIHSS score, CG48, and symptomatic ICH (BRANCH) corresponded with poor outcomes at 90 days; the area under the curve value was > 0.79. CONCLUSIONS: Failure of blood glucose values to decrease in the first 48 hours after AIS intervention correlated with poor 90-day outcomes in nondiabetic patients. The BRANCH scale shows promise as a simple prognostication tool after endovascular therapy for AIS, and it merits prospective validation.

Intra-arterial thrombolysis or stent placement during endovascular treatment for acute ischemic stroke leads to the highest recanalization rate: results of a multicenter retrospective study.

BACKGROUND: Reperfusion therapy for acute ischemic stroke (AIS) is rapidly evolving, with the development of multiple endovascular modalities that can be used alone or in combination. OBJECTIVE: To determine which pharmacologic or mechanical modality may be associated with increased rates of recanalization. METHODS: A cohort of 1122 patients with AIS involving the anterior circulation treated at 13 stroke centers underwent intra-arterial (IA) therapy within 8 hours of symptom onset. Demographic information, admission National Institutes of Health Stroke Scale (NIHSS), mechanical and pharmacologic treatments used, recanalization grade, and hemorrhagic complications were recorded. RESULTS: The mean age was 67 ± 16 years and the median NIHSS was 17. The sites of arterial occlusion before treatment were M1 middle cerebral artery (MCA) in 561 (50%) patients, carotid terminus in 214 (19%) patients, M2 MCA in 171 (15%) patients, tandem occlusions in 141 (13%) patients, and isolated extracranial internal carotid artery occlusion in 35 (3%) patients. Therapeutic interventions included multimodal therapy in 584 (52%) patients, pharmacologic therapy only in 264 (24%) patients, and mechanical therapy only in 274 (24%) patients. Patients treated with multimodal therapy had a significantly higher Thrombolysis in Myocardial Infarction 2 or 3 recanalization rate (435 patients [74%]) compared with pharmacologic therapy only (160 patients, [61%]) or mechanical only therapy (173 patients [63%]), P<.001. In binary logistic regression modeling, independent predictors of Thrombolysis in Myocardial Infarction 2 or 3 recanalization were use of IA thrombolytic OR 1.58 (1.21-2.08), P<.001 and stent deployment 1.91 (1.23-2.96), P<.001. CONCLUSION: Multimodal therapy has significantly higher recanalization rates compared with pharmacologic or mechanical therapy. Among the individual treatment modalities, stent deployment or IA thrombolytics increase the chance of recanalization.

Stroke centers and regional networks: A blueprint for improving outcomes.

There are two essential ways that patients with stroke get the best possible outcomes. They get to the right place at the right time, and the right place is organized to treat stroke based on the most current evidence. This article discusses the essential components of a stroke center, the key aspects of stroke care, and a model for organizing regional networks for stroke care in the state of Missouri.

Conscious sedation versus general anesthesia during endovascular therapy for acute anterior circulation stroke: preliminary results from a retrospective, multicenter study.

BACKGROUND AND PURPOSE: Patients undergoing intra-arterial therapy (IAT) for acute ischemic stroke receive either general anesthesia (GA) or conscious sedation. GA may delay time to treatment, whereas conscious sedation may result in patient movement and compromise the safety of the procedure. We sought to determine whether there were differences in safety and outcomes in GA patients before initiation of IAT. METHODS: A cohort of 980 patients at 12 stroke centers underwent IAT for acute stroke between 2005 and 2009. Only patients with anterior circulation strokes due to large-vessel occlusion were included in the study. A binary logistic-regression model was used to determine independent predictors of good outcome and death. RESULTS: The mean age was 66+/-15 years and median National Institutes of Health Stroke Scale score was 17 (interquartile range, 13-20). The overall recanalization rate was 68% and the symptomatic hemorrhage rate was 9.2%. GA was used in 44% of patients with no differences in intracranial hemorrhage rates when compared with the conscious sedation group. The use of GA was associated with poorer neurologic outcome at 90 days (odds ratio=2.33; 95% CI, 1.63-3.44; P<0.0001) and higher mortality (odds ratio=1.68; 95% CI, 1.23-2.30; P<0.0001) compared with conscious sedation. CONCLUSIONS: Patients placed under GA during IAT for anterior circulation stroke appear to have a higher chance of poor neurologic outcome and mortality. There do not appear to be differences in hemorrhagic complications between the 2 groups. Future clinical trials with IAT can help elucidate the etiology of the differences in outcomes.

Ischemic stroke: prevention of complications and secondary prevention.

In stroke cases where there has been acute interventional therapy and in those where no intervention was possible, attention to prevention of complications and secondary stroke prevention can substantially improve outcomes. Standardized clinical tools such as clinical pathways and standing order sets as well as collaboration among highly trained nurses and physicians are essential in implementing best practices. This article summarizes the current evidence in relation to these very important aspects of stroke care.

Vertebrobasilar revascularization rates and outcomes in the MERCI and multi-MERCI trials.

OBJECTIVE: Mortality of 40% to 86% and good outcomes in only 13% to 21% of patients beg for treatment options for basilar occlusion. This study determined outcomes of patients with vertebrobasilar occlusion treated with mechanical embolus removal in cerebral ischemia (MERCI) retriever mechanical thrombectomy. METHODS: Patients with vertebrobasilar occlusion in the MERCI and Multi-MERCI trials received treatment up to 8 hours after symptom onset. Recanalization was determined after retriever use and adjunctive therapy. Mortality and good outcomes, modified Rankin scale score 0-3, were determined at 90 days in patients who were recanalized and not recanalized. RESULTS: Recanalization occurred in 21 of 27 (78%) patients. Mortality was 44% and good outcomes were seen in 41%. Patients with recanalization tended to have better outcomes than those without. CONCLUSIONS: Outcomes in patients with vertebrobasilar occlusions treated with the MERCI retriever compared favorably with natural history reports and tended to be better in those patients with recanalization.

Mechanical thrombectomy for acute ischemic stroke: final results of the Multi MERCI trial.

BACKGROUND AND PURPOSE: Endovascular mechanical thrombectomy may be used during acute ischemic stroke due to large vessel intracranial occlusion. First-generation MERCI devices achieved recanalization rates of 48% and, when coupled with intraarterial thrombolytic drugs, recanalization rates of 60% have been reported. Enhancements in embolectomy device design may improve recanalization rates. METHODS: Multi MERCI was an international, multicenter, prospective, single-arm trial of thrombectomy in patients with large vessel stroke treated within 8 hours of symptom onset. Patients with persistent large vessel occlusion after IV tissue plasminogen activator treatment were included. Once the newer generation (L5 Retriever) device became available, investigators were instructed to use the L5 Retriever to open vessels and could subsequently use older generation devices and/or intraarterial tissue plasminogen activator. Primary outcome was recanalization of the target vessel. RESULTS: One hundred sixty-four patients received thrombectomy and 131 were initially treated with the L5 Retriever. Mean age+/-SD was 68+/-16 years, and baseline median (interquartile range) National Institutes of Health Stroke Scale score was 19 (15 to 23). Treatment with the L5 Retriever resulted in successful recanalization in 75 of 131 (57.3%) treatable vessels and in 91 of 131 (69.5%) after adjunctive therapy (intraarterial tissue plasminogen activator, mechanical). Overall, favorable clinical outcomes (modified Rankin Scale 0 to 2) occurred in 36% and mortality was 34%; both outcomes were significantly related to vascular recanalization. Symptomatic intracerebral hemorrhage occurred in 16 patients (9.8%); 4 (2.4%) of these were parenchymal hematoma type II. Clinically significant procedural complications occurred in 9 (5.5%) patients. CONCLUSIONS: Higher rates of recanalization were associated with a newer generation thrombectomy device compared with first-generation devices, but these differences did not achieve statistical significance. Mortality trended lower and the proportion of good clinical outcomes trended higher, consistent with better recanalization.

Interventional stroke therapy: current state of the art and needs assessment.

The primary therapeutic strategy for ischemic stroke, as for MI patients, is early reperfusion. Improvement in stroke treatment will require dedicated stroke centers to emulate MI quality indicators such as minimizing the "door-to-balloon time". A critical element in achieving this goal will be organizing the existing multidisciplinary pool of carotid interventionalists to provide the endovascular component of the acute care for ischemic stroke patients.

Organizing regional networks to increase acute stroke intervention.

OBJECTIVES: Acute ischemic stroke is the second leading cause of death worldwide and the leading cause of adult disability in the United States (US). Thrombolytic therapy was proved effective, and approved for use, in the US by the Food and Drug Administration in 1996, yet 8 years later just 3-4% of stroke victims in the US are treated with tissue plasminogen activator. In order to understand how this figure can be substantially improved, it is important to evaluate the available therapies and systems of care, delineate the critical steps and the existing barriers in the process for successful intervention, and thoroughly understand the key components in the highly successful interventional stroke programs, especially regionalization of care. METHODS: A review of the available literature was carried out and interventional stroke data from the Mid America Brain and Stroke Institute at Saint Luke's Hospital (SLH) in Kansas City, Missouri, was analysed. RESULTS: There are several treatment strategies available for acute stroke intervention and more are likely to be developed. There is increasing interest in organizing and standardizing care for stroke. The steps in the process for successful intervention are understood and progress is being made in several areas of the country, but challenges remain in public education, directing emergency transport to 'stroke ready' hospitals and linking stroke experts to primary care providers. The Kansas City regional network linking primary care hospitals to the stroke team at SLH has been highly successful in substantially increasing the number of patients receiving acute stroke intervention. DISCUSSION: The stage is set for many more stroke victims to receive acute interventional therapy. However, these patients must present to hospitals equipped and staffed to render this therapy. Most stroke victims will go or be taken to the closest medical facility. Organizing regional networks linking primary care hospitals and physicians to comprehensive stroke centers staffed, and capable of providing the entire spectrum of acute stroke intervention will be essential in substantially increasing the number of stroke victims who actually receive acute interventional therapy. This article summarizes the evolving solutions to this challenge with specific data from the successful regional network developed around the Mid America Brain and Stroke Institute at Saint Luke's Hospital in Kansas City, Missouri, USA.