Treatment Strategies For Acute Stroke Research Articles

Imaging biomarkers in acute ischemic stroke trials: a systematic review.

Imaging biomarkers are increasingly used to provide a better understanding of the pathophysiology of acute ischemic stroke. However, this approach of routinely using imaging biomarkers to inform treatment decisions has yet to be translated into successful randomized trials. The aim of this study was to systematically review the use of imaging biomarkers in randomized controlled trials in patients with acute ischemic stroke, exploring the purposes for which the imaging biomarkers were used. We performed a systematic review of imaging biomarkers used in randomized controlled trials of acute ischemic stroke, in which a therapeutic intervention was trialed within 48 hours of symptom onset. Data bases searched included MEDLINE, EMBASE, strokecenter.org, and the Virtual International Stroke Trials Archive (1995-2014). Eighty-four studies met the criteria, of which 49 used imaging to select patients; 31, for subgroup analysis; and 49, as an outcome measure. Imaging biomarkers were broadly used for 8 purposes. There was marked heterogeneity in the definitions and uses of imaging biomarkers and significant publication bias among post hoc analyses. Imaging biomarkers offer the opportunity to refine the trial cohort by minimizing participant variation, to decrease sample size, and to personalize treatment approaches for those who stand to benefit most. However, within imaging modalities, there has been little consistency between stroke trials. Greater effort to prospectively use consistent imaging biomarkers should help improve the development of novel treatment strategies in acute stroke and improve comparison between studies.

Management of Hypertension in the Acute Phase of Stroke

An increase in arterial blood pressure (BP) is common following the onset of stroke. Although there is evidence suggesting that this acute elevation of BP is associated with a poor clinical outcome in both ischemic and hemorrhagic stroke patients, optimal treatment strategies are currently unknown. The management of BP in the first 24 hours following stroke lends itself to two competing rationales in both stroke sub-types. In ischemic stroke patients, BP reduction may improve outcome, potentially by reducing hemorrhagic transformation and edema formation. Conversely, antihypertensive therapy may also reduce cerebral blood flow (CBF) in the penumbra, exacerbating ischemic injury. Similarly, BP reduction may improve outcome in hemorrhagic stroke patients by preventing the expansion of the hematoma and reducing perihematoma edema. The perihematoma region has also been hypothesized to have ischemic penumbral properties, although the evidence for this is limited. Nonetheless, there is the potential for detrimental CBF compromise following BP reduction in hemorrhagic stroke as well. Recently, advanced neuro-imaging techniques have made it possible to test many of the hypotheses related to the etiology of BP elevation and optimal treatment strategies in acute stroke. This article summarizes concepts and evidence for different BP management strategies in both types of stroke. Keywords: blood pressure (BP), hemorrhagic stroke, ischemic stroke, cerebral blood flow (CBF), neuro-imaging techniques

Treatment of acute ischemic stroke: Part I: recanalization strategies.

In 1994, a special writing group of the Stroke Council of the AHA published guidelines for the management of patients with acute ischemic stroke.1 The guidelines, based on the best available evidence, focused primarily on the prevention and treatment of the complications of acute stroke such as cerebral edema and increased intracranial pressure, aspiration pneumonia, urinary tract infections, deep vein thrombosis and pulmonary embolism, decubiti, and seizures. The authors further concluded that “until more data are available, the use of heparin remains a matter of preference for the treating physician” and “that thrombolytic therapy is not currently recommended for the treatment of patients with acute ischemic stroke.”1 No supportive recommendations were given for any neuroprotective strategy, nor therapies given to stimulate neurological recovery. In the 8 years since these guidelines were published, a large number of randomized studies of treatment strategies for acute stroke have been completed. These trials have included thrombolytic agents given intravenously, intra-arterially, or both, antithrombotic and antiplatelet therapies, neuroprotective agents, pharmacological and mechanical therapies to stimulate neurological recovery, and the use of stroke units. In addition, many pilot studies of new therapies for acute stroke have been reported and are entering Phase II and Phase III studies. The current state of knowledge regarding the treatment of acute ischemic stroke that are based on these randomized studies can be summarized as follows. (1) Intravenous thrombolytic therapy, if administered within the first 3 hours after stroke, improves functional outcome after acute ischemic stroke. Even within the first 3 hours, the likelihood of an excellent outcome increases with earlier treatment. The effectiveness of thrombolytic therapy after 3 hours has yet to be conclusively demonstrated but studies are ongoing. (2) Intravascular intervention with medical therapies and mechanical devices is an active area of investigation. (3) Aspirin and other …

Metalloproteinase inhibition reduces thrombolytic (tissue plasminogen activator)-induced hemorrhage after thromboembolic stroke.

A potentially dangerous side effect associated with tissue plasminogen activator (tPA) use is cerebral hemorrhage. We have focused on developing drugs that could be administered with tPA to reduce the rate of hemorrhage. Since recent studies suggest that various matrix metalloproteinases (MMPs) are important in tumor necrosis factor-alpha production and membrane and vessel remodeling after ischemia, we investigated whether MMP inhibition affected the rate of hemorrhage and infarct production in the absence or presence of tPA treatment. We occluded the middle cerebral artery of New Zealand White rabbits with radiolabeled blood clots. Five minutes after embolization, we administered either the MMP inhibitor BB-94 (30 mg/kg SC) or its vehicle. Additional groups received BB-94 or vehicle in combination with tPA, administered 60 minutes after embolization (3.3 mg/kg tPA). After 48 hours, the rabbits were killed and brains were removed, immersion fixed for 1 week in 4% paraformaldehyde, and then cut into 5-mm coronal sections that were examined for the presence of hemorrhage, infarcts, and recanalization. Hemorrhage after embolic stroke was detected in 24% of the control group. tPA induced macroscopically visible hemorrhage in 77% of the tPA-treated group. The rabbits treated with BB-94 had an 18% incidence of hemorrhage (P:>0.05 compared with control). However, when the combination of BB-94 and tPA was administered to rabbits, there was only a 41% incidence of hemorrhage (compared with 77% in the tPA group; P:<0. 05). Both tPA and BB-94/tPA were similarly effective at lysing clots, at 49% and 35% (P:<0.05), respectively, compared with the 5% rate of lysis in the control group. There was a trend for a reduction in the number of infarcts, but it did not reach statistical significance. Our data suggest that MMP inhibition attenuates mechanisms involved in tPA-induced hemorrhage. This novel form of combination therapy may show promise as a treatment strategy for acute stroke.