For years, the central focus for emergency department (ED) physicians responding to a patient with suspected stroke was the golden window—the roughly three-hour period following a stroke where tissue plasminogen activator (tPA) is effective without risking bleeding in the brain. In recent months, research has shown the potential for extending the window and fine-tuning patient selection.

Shifting time frames

On Jan. 31, the American Stroke Association (ASA) released updated guidelines for the treatment of ischemic stroke, and stated certain eligible patients could safely receive tPA to dissolve a clot up to 4.5 hours after symptom onset. The guideline was based on the results of European trials, including the European Cooperative Acute Stroke Study.

The extension doesn’t apply to all patients, however, explains Edward C. Jauch, MD, director of the division of emergency medicine at the Medical University of South Carolina in Charleston. Patients older than 80 years old, those taking oral anticoagulants and those with a National Institutes of Health Stroke Scale score of 25 or higher are not recommended to receive tPA past three hours as its effectiveness in these populations is not well established.

But the golden window—which Jauch says is “probably a misnomer”—is really about treatment selection. Research indicates that imaging, rather than strict adherence to the clock, can provide valuable information for stroke treatment.

The top row shows a stroke on DWI/ADC which has some enhancement on post-contrast T1 imaging. The bottom row shows the perfusion deficit on a TTP map, the permeability image when not corrected for arrival time and the permeability image after arrival time correction. The green circles show corresponding areas of contrast leakage on the T1 post contrast and ATC permeability images. (DWI = diffusion weighted image, ADC = apparent diffusion coefficient, PWI = perfusion weighted image, TTP = time to peak, ATC = arrival time corrected).

Source: PLos One, Dec. 20, 2012.

MRI vs. CT … or both?

The standard for imaging patients with a suspected stroke is an immediate CT scan. While CT is sensitive to hemorrhages and offers good visualization of bony anatomy, its primary advantages over MRI are purely logistical—CT is widely available, cheaper and offers rapid image acquisition. 

However, newly developed advanced techniques may soon expand the benefits of CT. Preliminary results of the START trial, presented at the 2012 Society of NeuroInterventional Surgery annual meeting, showed CT angiography source images (CTA-SI) could help predict which stroke patients will benefit from endovascular therapy. Researchers, led by Don Frei, MD, of Radiology Imaging Associates at Swedish Medical Center in Denver, used the Alberta Stroke Program Early CT Score (ASPECTS), provided by CTA-SI, to inform treatment decisions rather than relying only on the golden window.

“There is robust scientific evidence supporting ASPECTS as a patient selection tool for endovascular stroke therapy,” says Frei. “MRI is a robust patient selector, but any delay in time to recanalization is detrimental to good outcomes. In our practice, [ASPECTS] is fast to acquire and easy to evaluate on the fly in selecting patients for recanalization.”

CTA-SIs can be quickly obtained following a non-contrast CT in the ED and can detect early ischemic changes while also predicting final infarct volume. They can depict hypo-attenuated regions of the brain due to reduction in cerebral blood volume or due to delays in contrast arrival.

Frei and colleagues hypothesized that physiologic imaging data might provide a better way to select patients, and preliminary results showed that providing physicians this information about patients’ circulation led to positive outcomes at 90 days in 46.7 percent of participants overall, and in 55 percent of patients with a small core infarct. This suggests the approach can be used to guide patient selection for endovascular treatment, particularly those who may be beyond the golden window.

CT may be the workhorse in stroke imaging, but even with advances in CT technique, MRI offers more detailed information about stroke patients. Researchers at Johns Hopkins School of Medicine in Baltimore, are hoping new types of MRI analysis lead to more individualized stroke treatment. Using dynamic susceptibility contrast imaging, a technique adapted from tumor imaging, the researchers can more accurately identify areas of damage in the blood-brain barrier.

Although the risk of post-tPA bleeding in the brain is highest after a patient has passed the golden window, roughly 6 percent of stroke patients are susceptible to bleeding even when tPA is administered within three hours.

One challenge was applying arrival time correction to MRI data. Dynamic susceptibility contrast imaging offers a metric for blood-brain barrier permeability, but there’s a hitch when it comes to stroke imaging. Under normal circumstances, contrast is assumed to go to all parts of the brain in a similar fashion, says Richard Leigh, MD, assistant professor of neurology and radiology at Johns Hopkins. “That works fine in a normal brain with good blood flow, but in stroke patients, the part of the tissue that you are most interested in often has fairly considerable delays in contrast delivery,” he explains. “We basically tried to remove the delay in contrast delivery with arrival time correction.” Arrival time correction takes into account delays in contrast circulation, allowing for more accurate measures of permeability.

The technique could help identify patients who are going to bleed when given tPA within the golden window, as well as standardize management of patients who arrive for treatment after the window has closed. These patients generally receive an intra-arterial procedure where the clot is removed mechanically, stenting or a direct injection of tPA into the clot. Determining which option is best is controversial and more information about damage to the blood-brain barrier and which patients are at risk of bleeding could improve treatment selection criteria, says Leigh.

Although CT and MRI offer advantages and techniques are advancing for both modalities, research has shown that for many hospitals the choice of how to proceed with stroke imaging is not an either/or proposition (see sidebar). Many patients undergo a CT scan as soon as they arrive in the ED because MRI is not immediately available, and then receive an MRI exam in the next 24 hours. The question then becomes, if the information from an MRI is valuable, should systems be designed to make MRI more available for stroke imaging?

Both the National Institutes of Health and Johns Hopkins have embraced the role of MRI for stroke patients, says Leigh. In fact, many hospitals have installed an MRI in the ED and are operating it 24/7, and once providers implement processes to make MRI more readily accessible to the ED and improve staffing, Leigh says the role of CT becomes “very questionable.”

The need for speed

One point is certain: the faster a stroke patient gets treatment, the better the outcome. Delays increase the extent of brain damage that causes paralysis and loss of speech following stroke.

“The entire system of care needs to be streamlined so whatever the final tool you’re using for reperfusion—whether it be drug or device—you need to shorten that window and compress it as tightly as possible to maximize the amount of salvageable brain,” says Jauch.

The new ASA guidelines solidified the benchmark door-to-needle time at 60 minutes or less, a figure Jauch says is very achievable with a commitment from providers. “It’s the responsibility of the hospital and the system to compress the time from arrival to the time of initiating treatment for appropriate patients.”

Lean process management techniques, initially developed to increase efficiency in Japanese car factories, are playing a major role in improving door-to-needle times for administering tPA at Washington University School of Medicine in St. Louis and its affiliated hospital, Barnes-Jewish Hospital. Jin-Moo Lee, MD, PhD, professor of neurology at Washington University, says lean techniques have made significant inroads in healthcare over the last decade.

“When it first appeared, it was kind of revolutionary,” says Lee. “The idea that we can apply process improvement techniques from car manufacturing to patient care [seemed] ridiculous, but there are many similar issues.”

One parallel is the regularity of the process. Late in 2010, a team of lean engineers employed by Barnes-Jewish met with all physicians and staff involved in stroke care and mapped out, minute-by-minute, every step of the stroke care process.

Once the process was mapped in such detail, it was easy to spot inefficiencies, says Lee. Three areas stood out as targets for improvement. First, when a patient suspected of having a stroke came to the ED, rather than get hooked up to monitors and have blood drawn, he or she would immediately be delivered to the CT scanner. The hospital also prioritized group tasks so nurses and physicians could work more in parallel, accomplishing tasks like inserting an IV and gathering medication simultaneously rather than in a long series of tasks. Finally, since lab results reporting could take up to 30 minutes, the stroke team implemented point-of-care testing for the most crucial lab values.

The process improvements were implemented in February 2011, and Barnes-Jewish saw its door-to-needle times drop from approximately 60 minutes to 38 minutes within the first month. These improved times have persisted thanks to monthly meetings where processes are reviewed, according to Lee.

With ultra-efficient process design and continued advances in stroke imaging, the view from the golden window is improving by the day.