Friday, December 2

Session I: The Science of Acute Stroke Intervention

Population Risk Changes: Forecasts and Speculation about the Future of Stroke
George Howard, PhD, University of Alabama School of Public Health, Birmingham, Alabama

While stroke incidence and mortality rates have steadily fallen for three decades, increases in the population over age 65 (i.e., the "graying of America") imply that there will be a substantial increase in the number of stroke events, but that the average age of stroke patients will be at substantially older ages. In addition, there are suggestions of changes in the prevalence of stroke risk factors in the general population. Hypertension has been long recognized as having the largest population attributable risk (PAR) for stroke (that is, it is the most important "cause" of stroke). The high PAR for hypertension is a product of a modest relative risk (approximately 2 times the risk when present) but a very high prevalence rate (over 50% in most adult populations). This is in contrast to other risk factors such as diabetes, which has a similar relative risk (also approximately 2 times risk) but a lower prevalence (approximately 25% in most adult populations) that result in a lower PAR. However, there is evidence of general population shift to lower prevalence of hypertension (a general shift to lower levels of SBP), while the obesity epidemic in the US appears to be increasing prevalence of diabetes. Collectively, this may imply a falling importance of hypertension and an increase in the importance of diabetes, as a risk factor for stroke; with associated potential changes in the presentation of the stroke event. Collectively, these population changes could imply changes in the presentation of stroke patients in the future.

Pathophysiologically Targeted Therapy of Acute Stroke: Brain And Beyond
Ulrich Dirnagl, MD, Center for Stroke Research, Berlin, Germany

Sudden occlusion of a major artery supplying the brain sets in motion a cascade of pathophysiological events which eventually lead to demise of brain tissue, neurological deficits, and possibly death. Pathophysiology may instruct us how to intercept this sequence of events. First and foremost, the perfusion deficit needs to be reversed by reperfusion. In parallel, hyperacute damage to neuronal elements and its spread to neighboring tissues with critical perfusion may be delayed or prevented pharmacologically by channel arrest or blockade. These measures need to also target other elements of the neurovascular unit, such as glial cells and endothelial cells. Administered in the hyperacute phase, these measures are highly effective in animal models of stroke, but the time window and potential side effects have so far prevented clinical proof of concept. Since secondary mechanisms of damage (apoptosis, inflammation) are activated within minutes of the event, but evolve over hours and possibly even days, they present attractive therapeutic targets and the potential to minimize the spread of the lesion, which may occur even after recanalization. Unfortunately, the few interventions tested clinically did not demonstrate efficacy. A third line of protection is based on the realization that the ischemic brain communicates with 'supersystems' outside the CNS, such as the immune, cardiovascular, and endocrine systems. This may have negative impact on outcome (e.g. infection, arrhythmias, sarcopenia). As the signaling is presently being unraveled and can be intercepted in the periphery (e.g. β-blockade), novel avenues of acute stroke treament are on the horizon.

The Penumbra: How Does Tissue Injury Evolve?
Wolf-Dieter Heiss, MD, Max-Planck Institute, Cologne, Germany

The ischemic penumbra defines tissue which is perfused below the level for functional failure but above the level leading to irreversible morphological damage. Penumbra tissue has the potential for functional recovery provided that local blood flow can be reestablished, but irreversible damage will develop without sufficient reperfusion depending on the interaction of severity and duration of ischemia. Differences in selective vulnerability of neurons as well as differences in perfusion in small tissue compartments are responsible for a considerable heterogeneity in patterns of injury.
 
With acute flows below the threshold of energy required for maintenance of basic housekeeping (20 % of pre-occlusion values), injury in the core is a direct consequence of energy failure resulting in terminal depolarization of cells, and is established within a few minutes after onset of ischemia. During the subsequent subacute phase the irreversible damage expands into the penumbra: Multiple electrical and biological disturbances interact in the progression of irreversible damage. They are triggered by periinfarct spreading depression-like depolarizations (PIDs), which require increased energy for activated ion exchange pumps. The increased glucose and oxygen demand cannot be met by the restricted flow to the penumbra leading to hypoxia and stepwise increase in lactate. The pathogenetic cascade triggered includes among others: release of excitatory and inhibitory neurotransmitters, activation of ion channels, influx of calcium, free radical formation, nitric oxide generation. Usually within 6 to 8 hours, all the penumbra is converted into irreversible infarct. In a delayed phase, secondary phenomena may contribute to additional tissue damage.

How Early Tissue Injury and Intervention Promote Recovery after Stroke
Eng H. Lo, PhD, Massachusetts General Hospital, Boston

Many molecular mechanisms have been defined to explain the acute pathophysiology of stroke. However, recent emerging data now suggest that targeting these acute pathways may not be as simple as originally thought. Mediators that trigger brain injury during the early stages of stroke evolution may, surprisingly, be involved in promoting recovery during delayed stages after stroke. This biphasic nature of neurovascular and gliovascular responses may be critical for mediating the transition zones between initial injury and subsequent repair as the penumbra succumbs and remodels over time. Further investigation of these biphasic mechanisms should be essential for the optimal development of stroke therapeutics.

Data Blitz Presentations

Current Treatment of Basilar Occlusion
P. J. Lindsberg, Helsinki University Central Hospital, Helsinki, Finland

Basilar artery occlusion (BAO) is associated with high mortality (85–95%) if recanalization does not occur. Evidence of the efficacy of different therapy protocols of intravenous (IVT) or intra-arterial thrombolysis (IAT) and/or mechanical endovascular treatment is based on retrospective or prospective patient cohorts, since RCTs do not exist.
 
In a systematic analysis, BAO treated with IVT (76) and IAT (344) had equal odds of death or dependency: 78% after IVT and 76% after IAT (Stroke 2006;37:922). Good outcome was reached by 24% with IAT and by 22% with IVT. Recanalization occurred more frequently after IAT (65%) than after IVT (53%; P=0.05). In the absence of recanalization only 2% reached good outcome.
 
The time-window for recanalization therapies in BAO is not well-established. In Helsinki, IVT or IAT is applied within 12 hours after sudden onset BAO and within 48 hours in gradually progressive BAO (Stroke 2011;42:2175). After IVT (N=116), favorable outcome (mRS 0–3) was reached in 34% of patients treated within 6 hours, in 24% within 6–12 hours and in 19% above 12 hours. The rates of very poor outcome (mRS 5–6) were quite similar in the three time groups: 51%, 55% and 52%, respectively. Recanalization occurred in 76%, 58% and 58%, respectively.
 
Meaningful survival in BAO necessitates urgent recanalization and this requires rapid access to IVT or IAT. 'Bridging' protocols have been introduced where rescue therapies such as endovascular thrombolysis and on-demand mechanical thrombectomy or angioplasty are used. Multimodal imaging techniques should be used to choose the best therapeutic option individually.
 
Coauthors: T. Sairanen, D. Strbian, and M. Kaste, Helsinki University Central Hospital.

Basilar Artery Occlusion: Time for a Randomised Trial?
Wouter Schonewille, MD, University Medical Center, Utrecht, Netherlands

Despite recent advances in the treatment of acute stroke, the rate of death or disability associated with basilar artery occlusion (BAO) is almost 80%. Recently our study group reported the results of the Basilar Artery International Cooperation Study (BASICS), a prospective registry of patients with an acute symptomatic basilar artery occlusion. Our observations in the BASICS registry based on data of over 600 patients underscore that we continue to lack a proven treatment modality for patients with an acute BAO and that current clinical practice varies widely. Furthermore, the often-held assumption that IA therapy is superior to IV thrombolysis in patients with an acute symptomatic BAO is challenged by our data. The BASICS registry was observational and has all the limitations of a non-randomised study. Interpretation of the results is hampered by the lack of a standard treatment protocol for patients who were entered the study. As the IA treatment approach becomes increasingly available and utilized throughout the world, a large randomised controlled phase III trial investigating the added value of this therapy after IV thrombolysis in patients with an acute symptomatic BAO is a high priority. We believe that the results of the registry have shown sufficient evidence of equipoise to justify the performance of the BASICS trial in which patients are randomised between IV thrombolysis alone vs. IV thrombolysis followed by IA therapy.
 
Presented on behalf of the BASICS study group.
 
Coauthors: Patrik Michel, Centre Hospitalier Universitaire Vaudois, Lausanne; Christine Wijman, Stanford Stroke Center, Palo Alto.

Third International Stroke Trial of Intravenous Thrombolysis with IV rtPA in Acute Ischaemic Stroke: Baseline Characteristics of the 3035 Patients Randomised
Gord Gubitz, MD, Dalhousie University, Halifax

Background: intravenous (i.v.) rtPA is approved for patients with acute ischaemic stroke who meet strictly defined criteria. IST-3 sought to determine whether a wider range of patients might benefit.
 
Design: International, multi-centre, prospective, randomized, open, blinded endpoint (PROBE) trial of i.v. rtPA in acute ischaemic stroke. Suitable patients had to be assessed and able to be randomised and start treatment within 6 hours of developing symptoms, and brain imaging must have excluded intracerebral haemorrhage and stroke mimics.
 
Results: Recruitment closed 31st July 2011 with 3035 patients included, of whom only 61 (2%) met the 2003 European approval criteria for thrombolysis. 914 (30%) were in AF. 1617 (53%) were aged 80 years or over. NIHSS scores were: 0–5 (612), 6–20 (1995), 21–35 (426) patients. Times to randomisation were: 0–3hrs 849 (28%); 3–4.5 hrs 1178 (39%); 4.5–6 hrs 1007 (33%). 1 patient was randomised after 6 hrs. Patients randomised at earlier time points hours of onset were significantly (p < 0.0001) more likely to have a more severe neurological deficit and were significantly older (p < 0.0001) than those randomised later. Main outcome results will be presented May 2012.
 
Conclusion: The trial participants form a population of patients that will provide evidence on the balance of risk and benefit of iv rt-PA among patients who do not clearly meet the approved indications, especially patients those aged >80 years, an age group which had largely been excluded from previous randomised trials. Trial registration ISRCTN25765518.
 
Presented on behalf of the IST-3 collaborative group.
 
Coauthors: Peter Sandercock and Joanna Wardlaw, University of Edinburgh; Richard Lindley, The George Institute for Global Health, University of Sydney.

Lunchtime Workshop: How to Make Acute Intervention More Widely Available

Improving Public Education and Reaction to Stroke Symptoms
Mark J. Alberts, MD, Northwestern University Feinberg School of Medicine, Chicago, Illinois

The lack of recognition and poor or delayed reaction to stroke symptoms are major reasons for the late presentation of patients with an acute stroke for timely medical care. This is a multi-factorial problem. Poor public understanding of the meaning of stroke symptoms is a contribution factor, while poor processing and reasoning that is actually caused by the stroke are also important elements. Prior studies have demonstrated that an intense and focused multi-faceted educational campaign can reduce these time delays and increase the number of patients who seek care in a timely fashion. Any successful educational program must be tailored to meet the targeted population in terms of language, content, and format. Furthermore, such efforts need to be repetitive, since presentation times tend to regress to baseline within a few months of the cessation of such programs.
 
These efforts are made even more challenging since, on average, the typical layperson is unlikely to encounter an acute stroke patient in their lifetime. Other successful public education and reaction campaigns (using seat belts, safe sex, etc.) have targeted behaviors that are fairly frequent and have included clear consequences for not complying with the preferred act. The very nature of stroke, being relatively uncommon on a population basis, having heterogeneous presenting symptoms, and the lack of pain, all combine to make public stroke education a continuing challenge. Making use of social media, the Internet, and individual emergency alert services, in addition to intense and continuous mass media efforts, may be useful in improving public recognition and reaction to acute stroke symptoms.

How to Organize Pre-Hospital Services to Save Time
William G. Barsan, MD, University of Michigan Hospital, Ann Arbor, Michigan

For patients with acute stroke, time is brain. Thrombolytic therapy for ischemic stroke can significantly improve outcome when given within 3 hours of stroke onset, but currently only 2–5% of patients with ischemic stroke receive thrombolytic therapy. Delayed recognition of stroke and delayed arrival to the hospital are the major reasons for exclusion from treatment.
 
Once patients arrive at the hospital, AHA guidelines recommend that patients should get a non-contrast head CT within 25 minutes of arrival and optimal door to needle time should be 60 minutes or less. Timely and appropriate care from emergency medical services (EMS) can play a major role in reducing the time from stroke onset to thrombolytic treatment.
 
Numerous studies have shown that patients arriving by EMS arrive at the hospital more quickly than by any other means and there have been major efforts to educate the public on the signs and symptoms of acute stroke (brain attack) and encourage calling 911. Training programs for EMS dispatchers have shown that dispatch accuracy for stroke can be improved and several prehospital stroke scales have been developed to help EMS personnel recognize stroke more accurately in the field. Finally, multiple studies have demonstrated that when EMS notifies the hospital of a potential stroke patient arrival, the time to stroke recognition, time to CT and time to IV rtPA treatment can be significantly reduced.
 
Adequate tools for stroke recognition and EMS training can also open the door to prehospital delivery of treatment for acute stroke. The FAST-MAG study has shown that stroke patients can be adequately identified and treated in the field with a neuroprotective agent much faster than delaying treatment until hospital arrival. Future EMS studies are also needed to determine optimal care for stroke patients in the field regarding blood glucose, oxygen and blood pressure management.

How to Organize the ER to Save Time
Edward C. Jauch, MD, MS, FAHA, FACEP, Medical University of South Carolina, Charleston, South Carolina

Effective and efficient management of all forms of time-sensitive emergencies is critical; central to this is Emergency Department (ED) organization and preparation. Organization alone, however, is not a substitute for physician passion. With few minutes to spare in the delivery of acute therapies, organized systems of care must already exist and be well practiced for optimal patient outcomes. Organized stroke care is a top down process—regional stroke organization, EMS organization, and Hospital/ED organization. Each cannot work effectively without the others in place; they are intimately interconnected. Assuming regional and EMS stroke systems are in place, ED organization is the final hurdle. Organization in healthcare is often passive—a cool term but meaningless in the absence of a champion. Protocols, order sets, laminated cards, practice runs, group pagers, doughnut bribes, and daily meetings are necessary, but alone are not sufficient. A champion must be a true passionate champion, be in the ED on a daily basis, and work to weave the many members of the stroke team together. Their presence during EMS arrival, CT prioritization, decision making, and disposition is key, and they need to facilitate pushing the acute stroke patient through the process. Equally so, they must be proactively involved in providing feedback to all groups and promote the stroke program within the hospital and regional health care system. Expecting a bill board and certification badge to produce optimal patient outcomes is unrealistic and a disservice to patients—the hospital must invest and support a champion to oversee organization and maintenance of its resources.

Session II: Clinical Management of Medical Issues in the Acute Setting

Optimization of Patient Selection — Acute Image Acquisition and Relation to Pathophysiology
Andrew Demchuk, MD, FRCPC, University of Calgary, Calgary, Canada

Stroke is a very heterogeneous disease, which limits most stroke treatments’ efficacy unless mega-trials involving thousands of patients are performed or highly selected imaging based approaches are adopted. Multimodal MRI or NCCT/CT bolus based evaluation both hold great potential in imaging based selection trials. Both provide reasonable “snapshots in time” to determine the four critical pathophysiologic elements of acute stroke: (1) the presence of hemorrhage; (2) presence and extent of an intravascular thrombus that can be treated with thrombolysis or thrombectomy; (3) presence and size of a core of irreversibly infarcted tissue; and (4) presence of hypoperfused tissue at risk for subsequent infarction without reperfusion.
MRI is the more sophisticated approach but is limited by access, additional preparatory time requirements, and contraindications. CT is much faster and widely available, with CT-angiography (CTA) providing conventional angiogram-like visualization of the entire arterial tree. Imaging based selection trials to date have focused on MRI based PI/DWI volume mismatch to define the target population with salvageable penumbra. Given negative results in clinical trials, a mismatch volume of only 20% (PI>DWI) may not be the correct selection criteria. Further standardization and refinements of perfusion measurements and penumbral definitions are still needed for MR and CT perfusion. An alternative for image based selection is a simplified approach applying a NCCT/CTA “good CT”-occlusion paradigm. DWI is more sensitive to ischemia detection compared to NCCT due to better discrimination of small volume infarcts; however, when a systematic ASPECTS approach is used in acute disabling stroke, NCCT is similar to DWI to measuring infarct core extent. Critics of the “good CT”-occlusion paradigm would argue that penumbra is the region of brain tissue at risk of infarction that should be identified for treatment decision making, which is not possible to visualize accurately with a NCCT-CTA paradigm. We would counter with the fact that penumbra appears to remain quite constant and immediately surround the ischemic core. Ischemic core is the key pathophysiologic element which can be highly variable in size. It represents the major early determinant of clinical outcome regardless of acute stroke treatment. CTA, if bolus timing standardized, can also evaluate collateral blood flow critical to estimating tissue survival and can most accurately estimate the extent of thrombus burden, which is the major determinant of systemic thrombolysis recanalization success. The time has arrived to evolve acute stroke clinical trial design to more focused imaging based selection with refinements to the tissue at risk/core mismatch approach using MR and CT perfusion. Alternatively, a fast and widely available NCCT/CTA based “good CT”-occlusion approach may be all that is required, especially with the additional information on intravascular thrombus burden and collaterals that it provides. Standardization of bolus timing and investigator training in EIC interpretation remain barriers, however.

Hyperglycemia and Ischemic Stroke: The SHINE Trial

Karen C. Johnston, MD, MSc, University of Virginia, Charlottesville, Virginia

Hyperglycemia is common in acute stroke patients. Ischemic stroke patients with hyperglycemia have worse outcomes than those with euglycemia. There is clinical equipoise regarding how hyperglycemia should be managed in acute ischemic stroke patients. Two NIH funded, middle phase trials have demonstrated safety and feasibility of comparing IV insulin therapy for tight glucose control to standard sliding scale subcutaneous insulin therapy. The Stroke Hyperglycemia Insulin Network Effort (SHINE) Trial is an NIH-NINDS funded phase 3 efficacy trial that will assess the safety and efficacy of glucose control (80–130 mg/dL) using insulin infusion versus standard sliding scale insulin with target glucose <180 mg/dL. Approximately1400 hyperglycemic patients will be enrolled. Patients must be enrolled within 12 hours of stroke symptom onset and within 3 hours of hospital arrival. IV and IA thrombolysis will be allowed. Patients will be stratified by NIHSS score and IV tPA. The primary outcome is favorable outcome by modified Rankin Scale score at 90 days. It has also been suggested that hyperglycemia may alter the hemorrhage rates in patients treated with thrombolysis. An opportunity to explore differential hemorrhage rates in post thrombolysis patients enrolled in the SHINE Trial may exist.

The SHINE Trial is funded by the NIH-NINDS (U01 NS069498)

Tissue Injury and Cerebral Blood Flow: The Case for Neuroprotection
Alastair M Buchan, MD, University of Oxford, Oxford, United Kingdom 

Ischemic tissue of acute stroke patients can be salvaged by thrombolysis, which allows a rapid return of oxygen and glucose to the brain. Pharmacological protection of neurons has shown much promise in more than a 1000 preclinical neuroprotective studies, but has unequivocally failed to translate to an efficacious therapy in the clinic. The confounding effects of neuroprotectants on physiological variables such as blood flow have contributed to this failure. Neurons, glia and endothelial cells form the neurovascular unit, a tightly regulated cellular network that controls cerebral blood flow. Due to this neurovascular coupling, compounds altering neuronal activity would affect blood flow, both during ischemia and reperfusion, and this would have a significant impact on injury. For example, targeting pathways that are central components of oxygen sensing, such as hypoxia inducible factor-1alpha (HIF-1alpha), can confer protection in animal models of focal ischemia, but the effect is at least partially mediated by improving cerebral blood flow. Since tissue injury is significantly correlated to the level of cerebral blood flow, neuroprotection may be associated with the increased delivery of oxygen and glucose rather than the biochemical prevention of cell death. In order to investigate pure neuroprotection independent of physiological variables, the global model of cerebral ischemia can be utilised. This model results in a uniform forebrain ischemic insult leading to the selective resistance of CA3 neurons in the hippocampus. Identifying the mechanisms responsible for this endogenous neuroprotection independent of physiological variables, has the potential for development of successful clinical therapies for stroke patients.

Combined Intravenous–Intra-arterial Treatments Approaches: IMS3
Joseph P. Broderick, MD, University of Cincinnati, Cincinnati, Ohio

A combined intravenous and intra-arterial approach to reperfusion provides the advantage of a rapid start of an effective therapy (IV t-PA) in any hospital emergency department with a CT scan, t-PA, and a trained physician; as well as potentially superior methods to recanalize occluded intracranial arteries via endovascular devices and additional intra-arterial t-PA. Endovascular approaches by themselves have the disadvantage of additional time to initiation of therapy and are more limited in their availability. Time to reperfusion has been demonstrated to be extremely important in both IV t-PA trials and endovascular pilot studies of combined therapy, with regards to clinical outcome. The combined approach is currently being tested in an NINDS-funded Phase III randomized trial, IMS III which has recruited 568 of 900 projected patients as of October, 2011. Other randomized trials of endovascular therapy are ongoing as well. IMS III is designed to test the approach of combined IV and endovascular therapy rather than a specific device, since technology continues to evolve. The use of combined therapy in clinical practice has also evolved with greater experience of standard dose IV t-PA prior to endovascular therapy. Despite great promise, endovascular therapy has not been demonstrated to be superior to IV t-PA in terms of clinical outcome. Completion of randomized trials of combined therapy or other endovascular approaches is critical to determine the clinical effectiveness of endovascular therapy and its proper role in clinicael practice.

Enhancing the Use of Thrombolysis
Geoffrey A Donnan, MD FRACP FRCP, Florey Neuroscience Institutes, University of Melbourne, Melbourne, Australia

Since thrombolysis was first shown to be effective for treating acute ischemic stroke, therapeutic uptake has been modest. Efforts are being directed towards rectifying this situation in a number of ways. First, strategies to enhance thrombolytic efficacy are being tested; these include intravenous and intra-arterial bridging protocols, sonothrombolysis, and the use of alternative thrombolytic agents. Second, means of extending the therapeutic time window in patients selected on the basis of imaging are being investigated in clinical trials. Third, attempts are underway to reduce the risk of symptomatic intracerebral hemorrhage and improving efficacy. This is being done by refining imaging selection criteria, and through the use of lower doses of tissue tPA as well as alternative thrombolytic agents such as tenectaplase. Last, improvements in prehospital management strategies are being introduced. Several of these issues will be discussed in more detail.

Treatment of Acute Ischemic Stroke: Systemic or Local?
Rüdiger von Kummer, MD, PhD, Technische Universität Dresden

In acute ischemic stroke, treatment delivery approach is still disputed. Many favor prompt treatment with IV rtPA after exclusion of intracranial hemorrhage with non-enhanced CT. They argue that the search for a more specific treatment with advanced brain imaging studies consumes the time period in which reperfusion therapy is beneficial. Intravenous rtPA has enhanced the proportion of patients without disabling stroke in 2 randomized controlled trials (RCT) by absolute 13% and 7%, an effect that disappeared within the first 6 hours of stroke onset. This effect was 15% in an RCT with IA pro-Urokinase. Patients with MCA occlusions being treated with IA urokinase in Bern within 6 hours of stroke onset had more frequently (29%) a favorable clinical outcome than patients being treated with IV rtPA within 3 hours (13%). A similar effect showed the combined IV-IA treatment with rtPA compared to a historical control group treated with IV rtPA only. Although the results of RCT directly comparing IV vs. IA treatment are not yet available, there is increasing evidence that arterial recanalization and brain tissue reperfusion are the key factors enabling good clinical outcome after ischemic stroke. It was shown that the probability of good clinical outcome is more than 70%, if angiographic reperfusion is achieved within 4 hours of stroke onset and declining thereafter. Many stroke patients may have better chances to benefit from advanced diagnostics and tailored treatment than from IV rtPA. We should provide the chances.

Kenote Address 2: How Baseline Severity Affects Safety and Efficacy Outcomes in Acute Intervention Trials
Philip B. Gorelick, MD, MPH, University of Illinois at Chicago

Baseline severity of stroke may be an important predictor of efficacy and safety outcomes in acute intervention trials. More severe stroke-related brain and blood vessel injury may predispose to less optimal clinical outcomes and more brain hemorrhage with recanalization/reperfusion therapies and other acute ischemic stroke therapies. In this discussion we will explore definitions of baseline variables and outcomes used to measure stroke severity, efficacy, and safety.
 
In addition, we will review select individual acute ischemic stroke intravenous thrombolytic studies such as the National Institute of Neurological Disorders and Stroke rt-PA Stroke Study and European Cooperative Acute Stroke Studies (ECASS), select neuroprotectant and endovascular clot retrieval studies, and large cooperative data bases such as the Virtual International Stroke Trials Archive (VISTA) and Safe Implementation of Treatment in Stroke-International Stroke Thrombolysis Registry (SITS-ISTR) to explore relationships between baseline stroke severity and efficacy and safety outcomes.
 
The NIH Stroke Scale and modified Rankin scale will be featured as major stroke outcome measures based on frequency of use and reliability, familiarity, adaptability, and comparability. We will discuss the role of potential key predictors of outcome such as baseline clinical stroke severity, age, time to treatment, and other variables. Although patients with more severe baseline stroke deficits and those who are older may be at higher risk of less optimal stroke outcomes and a more frequent risk of brain hemorrhage, intravenous thrombolytic therapy generally remains a beneficial treatment in these patients when compared to placebo.