Improving Quality of Life After a Stroke

The odds of surviving a stroke are greater than they’ve ever been, thanks to extensive research and the development of better treatments. But progress has been slower to address stroke’s aftereffects—the memory lapses and trouble forming words, anger and depression, limb weakness, and the heightened risk for a second, more dangerous—and potentially fatal—stroke.

Early, intensive, and comprehensive rehabilitation is essential to enhance function and minimize complications after a stroke. Extensive scientific research has focused on promoting post-stroke neuroplasticity—the ability of brain cells to form new connections—which is correlated with improved functional recovery. While this approach cannot repair the original brain damage caused by a stroke, there are strategies to assist individuals in managing the often-chronic residual effects.

“The rate of recovery—and the chances of preventing these problems—are highest in the first few days to months after the stroke,” says Nishant Kumar Mishra, MD, PhD, assistant professor of neurology at Yale School of Medicine (YSM) and stroke director at the VA Connecticut Healthcare System in West Haven. “Early neuropsychological and rehabilitation assessment after stroke is essential. This can inform the stroke team about the patient’s specific needs and provide personalized rehabilitation interventions that begin on day one or two while the patient remains in the hospital.”

YSM is recognized as a world leader in stroke, having established one of the first stroke centers in the United States in partnership with the VA Connecticut Healthcare System in West Haven. It has made significant contributions to research, becoming a key partner in the Southern New England Partnership in Stroke Research, Innovation and Treatment Center, a regional coordinating center for the National Institutes of Health’s StrokeNet. The Adams Neurosciences Center, scheduled to finish construction and open in 2027, will expand that care with two patient care towers in New Haven—which will provide inpatient services including a dedicated neurointensive care unit and stroke service with a patient- and family-centered approach to treatment and rehabilitation.

YSM’s experts include three researchers who seek to build on existing work around rehabilitation, and are involved in multisite studies they believe will lead to important contributions to long-term outcomes after stroke.

Rebecca DiBiase, MD, MPH, assistant professor of neurology at YSM, became interested in how to improve life after stroke when she started to get to know patients. “After the stroke is when you develop a long-term relationship with them, where you’re trying to figure out how you can get them back to doing things that they enjoy,” DiBiase says.

There are good reasons to start rehabilitation for these patients as quickly as possible after stroke, Dibiase says. “Part of what drew me to study the brain is that it’s not just a muscle or electricity,” she says. “It’s composed of networks of nerves that communicate with one another, and they’re wired in a complicated manner. When a stroke causes a part of your brain to basically become dead tissue, the networks must sort of form back roads around that area.” While experts are still learning more about these networks, one thing research shows is that “the faster we start rehab to help the brain form those networks, the better they’ll reconnect with each other and find a back road,” DiBiase says.

DiBiase is Yale’s principal investigator in a National Institutes of Health-funded clinical trial called VERIFY (Validation of Early Prognostic Data for Recovery Outcome after Stroke for Future, Higher Yield Trials). The study is looking at ways to address more quickly the loss of hand and arm mobility, which affects as many as 80% of people who have had an ischemic or hemorrhagic stroke. “This is a very rough estimate, but in a week of taking care of stroke patients in the hospital, if we see 30 patients, there’s a good chance that at least a quarter to half of them will have some sort of arm mobility problem,” DiBiase says.

The central hypothesis of the study is that survivors of stroke experience arm mobility issues in different ways, which suggests a potential need for different treatments. VERIFY’s goal is to create the first multicenter large-scale prospective dataset that includes clinical data, brain stimulation, and brain imaging measures taken during the acute stroke time window.

“We are testing different exams, basically, so that we can build a toolbox of ways we can quantify people’s ability to move their arms and hands,” DiBiase says, explaining that this information will lay the groundwork for interventional trials. The exams range from patient reports to putting electrodes on the patient’s arm and measuring how fast the electrical signal travels from the muscles. “Once we know which tests are best, we can apply those tools to trials in which we look at devices or medications for rehabilitation,” DiBiase says.

However, mobility is only one aspect of stroke recovery, says DiBiase. “I see patients who regain their movement and some sensation, and even their speech, but they still have a lot of concerns about brain fog, fatigue, and not being able to get through the workday like they used to,” she says. “We have a long way to go in terms of figuring out why that’s happening and what we can do to help.”

Mishra has a particular interest in post-stroke epilepsy, a common complication diagnosed when a person has at least one unprovoked epileptic seizure occurring seven or more days after their stroke. Having a seizure within the first seven days of a stroke increases the risk of developing post-stroke epilepsy, which is associated with higher mortality and worse cognitive outcomes.

But post-stroke epilepsy is an area in which there are still many questions, Mishra says. Before joining Yale, Mishra worked at several major stroke centers and the U.S. Food and Drug Administration, and he understood that he could achieve more by collaborating with other researchers focused on the same problem. In 2021, he and Patrick Kwan, MB BChir, PhD, of Monash University in Australia joined forces to launch the International Post-Stroke Epilepsy Research Consortium to accelerate discoveries on preventing epilepsy after stroke. The consortium holds an annual meeting and has attracted members from the United States and other countries, including Brazil, India, and Japan. “It creates an opportunity to discuss ideas and build collaborative research projects,” Mishra says.

Mishra says several of his projects have benefitted from his consortium collaborations, including a recent study published in Neurology in January 2025. The meta-analysis looked at the safety and efficacy of drugs used to treat seizures in people after ischemic or hemorrhagic strokes.

“There is significant variability as far as how well available drugs work,” says Mishra, who led a multi-institutional team to evaluate different medications used for post-stroke seizures, analyzing rates of adverse events, seizure recurrence, and drug discontinuation. “The drugs that came out most favorably in the analysis were levetiracetam and lamotrigine,” he says.

Going forward, Mishra’s focus will be on clinical trials that investigate whether the drugs can prevent post-stroke epileptogenesis—the process by which a previously healthy brain changes, leading to the development of epilepsy.

Meanwhile, there is still much work to be done, he says. “We need to highlight that post-stroke seizure is a problem that is underestimated, because certain seizures, such as behavioral seizures that can manifest as a lapse of awareness or cognitive impairment, may go undetected,” he says. “Patients, families, and general clinicians need to be aware of these characteristics.”

Richa Sharma, MD, MPH, was a teenager when her grandmother had strokes that left her with significant disability. Proper care and resources were not available in the village in India where her grandmother lived. “We didn’t know what caused her strokes in the first place or what risk factors she may have had that contributed,” Sharma says. “That really resonated with me and later carried me through all my medical training.”

Sharma, an associate professor of neurology at YSM, now wants to understand why so many strokes (up to one-quarter each year) occur in people who have had previous strokes. Understanding the etiology behind stroke can be diagnostically challenging, she says, but if you can pinpoint the cause of the first stroke, you’ll be better able to prevent a second, more dangerous one.

Sharma and her colleagues are evaluating routinely collected patient data to understand why particular people have acute ischemic strokes. And they’re doing this with an artificial intelligence tool they developed called StrokeClassifier, which they described in a paper published in npj Digital Medicine.

To build the AI tool, Sharma focused on data from various sources, including the clinical narrative and diagnostic tests recorded in a stroke patient’s electronic health record starting from the moment they arrive at the hospital. A pattern-recognition algorithm enabled the researchers to classify patients who had a stroke into groups with different contributing factors, such as large artery atherosclerosis or atrial fibrillation. That classification, says Sharma, can then inform what treatments might be most effective to prevent a second stroke.

Sharma is now working with Yale New Haven Health to develop an Epic medical record application called Polaris that will analyze a patient’s information and personalize treatment recommendations. “The result is an individualized, customized treatment plan for preventing a recurrent stroke,” she says.

“We hope to provide not just a diagnosis, but also the indicated therapy—what the guidelines recommend, what the level of evidence is, and where that evidence is drawn from,” Sharma says. Also, it is important to identify the other risk factors a patient may harbor that could contribute to a second stroke—which could include high cholesterol, high blood sugar, or active smoking. “We hope to map those factors to all the treatments that are guideline-recommended, to be implemented or at least discussed with the patient during the course of the hospital stay prior to discharge,” Sharma says.

DiBiase, Mishra, and Sharma agree that one of the greatest challenges in post-stroke rehabilitation is how to implement the approaches they are studying in all the locations throughout the country, and even worldwide, where people seek treatment for stroke. “Care is not uniform,” says Sharma; she notes that only one out of six patients having an ischemic stroke is treated by a board-certified vascular neurologist. “I want to help level the playing field for all clinicians caring for stroke patients by giving them the skill and confidence to be able to provide patients with the highest standard of personalized care.”