Stroke Management: A 30-Year Retrospective

Frieda Wiley

December 12, 2022

In 1993, managing patients with stroke had long remained an elusive and somewhat intimidating task for the neurological world. Previous efforts to treat the condition had produced more frustration than success, leaving clinicians and patients alike in despair for a solution. However, some successes in treating coronary thrombosis during that era rejuvenated researchers' efforts to crack the code. An international team of researchers had studied a Streptococcus derivative (streptokinase) and others had begun to study a natural substance termed tissue plasminogen activator (tPA) as thrombolytic agents to lyse coronary clots and to treat pulmonary embolism. The adverse event of excessive bleeding found in Australian studies done on streptokinase intervention in patients with stroke prompted researchers to contemplate use of tPA in stroke management.

The combination of tPA and advanced imaging technology led researchers to take a unique approach that would forever revolutionize stroke management, beginning in the early 1990s.

A group of German, Japanese, and American investigators began to research thrombolysis in acute stroke patients during the mid-1980s.

Dr Louis Caplan

"What was unique is that patients had a CT scan followed by a catheter angiogram," said Louis Caplan, MD, a senior member of the division of cerebrovascular disease at Beth Israel Deaconess Medical Center, Boston, professor of neurology at Harvard Medical School, Boston, and founder of the Harvard Stroke Registry at Beth Israel Deaconess Medical Center.

"If they had a blocked vessel, they got the drug, delivered either intravenously or intra-arterially."

The process involved keeping the catheter open after drug administration to determine whether the vessel had opened or remained occluded. The researchers learned which blocked vessels opened when the drug was given intravenously and which required direct introduction of the drug into the clots.

A group of investigators in the United States funded by the National Institute of Neurological Disease and Stroke then performed a randomized therapeutic trial of intravenous tPA given within 90 minutes and 180 minutes after stroke symptom onset. The study was reported in the New England Journal of Medicine. Soon thereafter, in 1995, the Food and Drug Administration approved the use of tPA following the inclusion and exclusion rules used in the NINDS trial.

After the FDA approved tPA in 1995, stroke management was never the same.

tPA Was Just One Factor in Optimizing Stroke Management

Despite the major therapeutic breakthrough with tPA's approval, it took the clinics, hospitals, and other acute care systems a while to catch up. "Neurologists and hospitals weren't ready for acute stroke intervention and proper stroke management in the mid-90s," Caplan recalled. "At the time, stroke wasn't at the forefront of treatment, general neurologists weren't trained, and there weren't enough stroke neurologists."

The preparation and training deficit was further exacerbated by low reimbursement for services. As a result, only about 5% of patients who were eligible for acute stroke management were treated with tPA.

According to Caplan, during the next 15-20 years, the accumulation of stroke data from MRI and CT vascular imaging clarified further which patients, with what extent of infarction, with which blocked vessels, would be good candidates for treatment.

More patients received interventional treatment using catheters directed into the area of clotting in attempt to remove the blockages. In addition, information regarding intervention at different periods (10-16 hours, up to 24 hours) and conditions (for example, patients with varying degrees of disability, infarct) were tested.

Eventually, hospitals became more attuned to emergency stroke treatment. More neurologists became trained, more stroke centers emerged, and clinicians enjoyed the benefit of technological advancements that allowed them to explore perfusion.

While Decentralized Care Enhances Outcomes in Stroke Management, More Progress Is Needed

As of early 2023, stroke is one of the leading emergency diagnoses, and patients have access to primary and secondary stroke centers that are sprinkled throughout the United States. As impressive as the feat may seem, health care systems still have major strides to make to truly optimize therapy and outcomes in this patient population.

For example, location and access remain important issues. Secondary centers are typically located in large, metropolitan areas. While an urban location makes a primary center geographically more accessible to a larger patient population, traffic frequently hinders door-to-door access.

In the case of rural centers, distance can retard access, but they also face the challenges of how to route patients – especially patients who require more specialized care offered by secondary centers. Fortunately, primary centers have some ways to help better support their patients.

"One thing that happened is that primary centers made agreements with secondary centers via telemedicine to determine whether patients should be treated at the primary center or whether they should be routed to the higher-level center. These arrangements were termed 'spoke and wheel,' " Caplan told this publication.

However, not all patients who are candidates for transport to a secondary center are able to be transported. In such cases, primary centers can use telemedicine to collaborate with secondary centers for support.

Logistics aside, perhaps today's greatest challenge for clinicians is ensuring their patients and families receive education to increase their awareness of stroke centers as an important option for treatment and outcome optimization. Many patients and their loved ones do not realize that these centers exist or how to utilize them if and when the time comes.

Right now, some cities have stroke ambulances staffed with physicians to treat patients in the field. This decentralized model helps address access burdens such as door-to-needle delays and transportation while improving survival and recovery. Caplan said these services are available in Munich, and in a few select U.S. cities such as Cleveland and Houston, which helped pioneer the concept.

Better Access in the Future?

Looking ahead, Caplan seems optimistic about how stroke management will continue to evolve. Many cities will have stroke ambulances to provide on-site care, while stroke institutions will improve their cross-collaborative efforts to support their patient populations.

At the crux of cross-collaboration lies enhanced communication between peripheral and urban hospitals.

"Peripheral and urban hospitals and state organizations will engage in smoother integration to figure out when to take patient to the bigger hospitals," Caplan said. "I also believe we will see greater emphasis on rehabilitation and recovery."

As promising as the future looks, only time will tell.

This article originally appeared on, part of the Medscape Professional Network.


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