Stroke of the Future
In 20 years, stem cells, genetics and robotics will get patients back on their feet after a blood clot in the brainBy Janet Wilson, Illustrations by Don Dufur
Someone in the U.S. dies from stroke about every four minutes. Since 1995, it has dropped from being the third-highest cause of death to the fifth-highest, thanks to public education, rapid response systems pioneered by UCI and others, and advances in powerful drugs to dissolve clots and tools to remove them. However, stroke remains a leading cause of disability. One in five women will suffer one, according to the Centers for Disease Control & Prevention, and nearly 25 percent occur in people under the age of 65. Each year, approximately 600 patients are treated by UCI’s stroke specialists.
In this story, we follow the progress of a hypothetical stroke patient 20 years from now, when many life-altering advances could be realized, from stem cell therapy to customized treatment based on genetic profiling. These possibilities are noted throughout the story in italics.
Day One: The Stroke
My 7-year-old, Sonya, hears me fall as I turn off the water. I lie there in the shower; I can’t move my left leg or arm. She runs in, stares and pulls a towel over me. Just as we practiced if there was ever an emergency, she finds my cellphone in my purse, waves it in front of my eye to unlock it and calls for help.
When the emergency crew arrives, they ask me my name, my age, where I am and what day it is.
“My name is Leticia Lopez. I live in Norco, and I’m 45,” I whisper. “It’s Sunday, Oct. 26, 2036.”
They ask me to stick my tongue out straight. I can’t. They ask me to lift my left arm. I can’t. The taller one says there’s no time to dress me. They lift me, dripping, onto the gurney and into the ambulance.
At Corona Regional Medical Center, they take a CT scan right away. It’s so noisy and cold. I just want to curl up and sleep. A nurse turns a video monitor toward me.
“Leticia, I’m Dr. Ali Razmara with the University of California, Irvine,” says the man on the screen. “I’m a neurologist. You’ve had an ischemic stroke. A blood clot has formed in your brain. We’re going to try to stop the damage.”
I’m Joseph, and I’m 46. I met my wife 20 years ago at the Cerritos mall, where I was a security guard at the time. She was doing temporary Christmas work. “I have to act fast; I hear you’re leaving soon,” I told her.
People still chuckle at that story. We have three kids: Robert, 17, Edward, 16 (we call him Eddie), and Sonya. This afternoon I’m driving to Riverside to show a client a house we’ve listed. It’s been a rough few years, the worst since the Great Recession of 2007-09, but thankfully, the real estate market is coming back. My phone buzzes. It’s Sonya.
“Daddy, Mommy fell and she can’t get up.” That’s weird. She was fine when I left half an hour ago. Maybe she broke her leg. Sonya sounds calm. I’m so proud of her. I call 911 and turn around off the freeway. At the medical center, I run from the parking lot into the emergency room. There are a whole bunch of doctors and nurses around Leticia.
I hear a voice, so calm, so soothing. I can’t tell where it’s coming from. Someone turns a video monitor toward me.
“Mr. Lopez, I’m Dr. Ali Razmara with UCI. Your wife has had an ischemic stroke because of a thrombus, a blood clot that’s blocking part of her brain. I want to start her on tPA, a tissue plasminogen activator.”
The drug will spread through her brain and could break up the clot, he says. The first four to six hours are critical. Billions of cells could be lost if she doesn’t receive treatment.
“We have to act fast; we don’t want her leaving us,” he says.
“They quiz me about any warning signs: Slurred speech, stomachache, headache, uneven walking? There were none.”
They quiz me about any warning signs: Slurred speech, stomachache, headache, uneven walking? There were none. She was fine at 2 o’clock – I kissed her goodbye as she was about to get in the shower. That’s good, they say. It’s barely 3 o’clock. There’s a slight risk the tPA could cause internal bleeding, but more likely it could save her life. A nurse hands me consent forms and prepares an IV drip.
Dr. Razmara comes back on the telestroke screen – that’s what they call it, like Skyping for doctors to diagnose and treat patients.
“We’d like to airlift Leticia to UC Irvine Medical Center,” he says. “We’re a nationally certified comprehensive stroke center, and we’ve got good specialists here. It looks like your wife has had a pretty major stroke.”
“Yes,” I say. “Thank you.”
I pick up the kids, and when we arrive in Orange, Dr. Razmara hustles us through low-ceilinged hallways and double doors. They ask the kids to stay in the waiting room. Leticia looks at me and closes her eyes.
An IV is attached to her right arm; they’re pumping in the clot-busting tPA and other drugs to protect her neurons from permanent damage. An attendant attaches metal clamps – robotic stimulators – along Leticia’s left side, on her foot, fingers, lips and cheek. They will pulse rapidly on her skin, which could reorganize the blood flow in her brain, opening alternate arteries wide to rush in oxygen and reverse the stroke.
Dr. Shuichi Suzuki, a vascular neurologist, introduces himself. He wants to perform a thrombectomy to remove the clot. He will thread a tiny tube through an artery in Leticia’s groin all the way up to her brain – dodging major organs, monitoring every millimeter on a live computer screen, backing out a bit and going in again, if needed – until he reaches the right spot and then will suck the clot or its remnants down the tube and out of her body. She’ll receive local anesthesia. There are major risks.
“Yes,” I say. “Do it. Please.”
My eyelids feel like they have gum or glue stuck to them. I’m so thirsty, but they won’t give me water. They’re worried I can’t swallow. My right thigh hurts. Joseph explains why. The clot is out of me. “You’re doing great,” he says.
I can’t move my left side. I’m tethered to a catheter, a feeding tube and an IV, and I can’t stop drooling. Other than that, I’m doing great.
Leticia is sleeping. I feel like the day has been a series of miracles.
Day Two: In-Patient
Dr. Wengui Yu says the medication and tactile stimulation helped, but there is damage to Leticia’s brain and it’s swelling. They want to do a craniotomy the next day, creating a small flap in the skull to relieve the pressure. “Yes, whatever you think is best,” I say again. “Thank you for everything.”
A resident hurries in and whispers. Dr. Yu looks sad when he turns to me. Leticia’s brain has begun swelling rapidly. It doesn’t look good. They have one option, he explains, but it’s very high-risk. They can remove a large section of her skull.
I don’t know what to do. “Can you give me a minute?” I say. My cellphone rings. I hear a calm voice. It’s Dr. Razmara; the resident paged him. He tells me that if it was his sister or mother, he would do the surgery – yes, knowing the risk. It answers my question.
We stay by the elevator downstairs from the operating room for hours. My phone buzzes constantly – worried friends, family and our pastor.
Near midnight the elevator door finally opens and the surgeon emerges. I’ll never forget that smile. Oh, my God, she’s going to be okay.
“Mr. Lopez, the swelling went down much faster than we thought it would, as soon as we gave her brain some breathing room,” she says.
The left side of my head hurts. It’s been shaved, and the hair in the back feels stiff, like it has dried blood in it. My beautiful curls are gone.
Day Three: Advanced Medical Treatment
Dr. Steven Cramer visits me in my room the next morning. He says we’ve made it through the crisis. We’re on our way. He explains that he’s both a medical doctor and a researcher specializing in brain injuries, particularly strokes.
“Your brain is already galvanized for repair,” he says. “After a stroke, it goes to work right away trying to rebuild the smoldering ruins. You don’t even have to think about it. But we can help the process a lot.”
UCI is on the front lines of stroke care, he explains. There have been tremendous advances in the 21st century by interdisciplinary researchers here and elsewhere to help people recover from stroke: neurointerventionists, engineers, occupational therapists, psychologists, data programmers, biologists, dance specialists, gaming theorists, statisticians. My head swims, but I listen.
“You’re pretty lucky, though you may not think so right now,” Dr. Cramer says. “We’re still tackling how to get treatments to people in rural and poor parts of the world.”
Most people think only children’s brains can change, he says, but over the last several decades, scientists have found that adult brains also have “plasticity,” meaning they have an extraordinary ability to change their structure and function.
“When part of the brain has been blown up and you’ve suffered damage that’s causing paralysis, say, you want the remaining elements to start communicating differently, in order to get your limbs working again,” he says.
By combining stem cell therapy in the next few days with intensive physical rehabilitation for the next month or two, they will deliver a one-two punch to the stroke’s worst effects. Dr. Cramer says that my brain has a lot of potential for rewiring itself if I work hard and that I have a strong chance of a full recovery. Parts of it will even be fun.
That afternoon, they take cell samples from my skin that have not developed for specific body functions. Using my own cells reduces the risk that my body will reject the treatment. They make a cocktail of those and specialized drugs and inject them into the injured area. They implant a tiny device to stimulate brain activity. Both treatments should foster new electrical connections to send signals to nerve endings throughout my body. Part of my right brain isn’t working, but just like a car detours off the 405 when it’s jammed to the 55 and 5 freeways, my central and left brain will find new paths. “This is what we mean by plasticity,” the surgeon explains.
They also culture my bone marrow cells to make them multiply and administer them intravenously to improve immunity and healing.
That night, I dream I’m back in high school, tap-dancing on a stage that gets higher and higher. Sophia joins me in her witch costume. I realize it’s nearly Halloween. “You’re my cute witch,” I tell her. “You’re my hero.”
A ‘Spoke and Hub’ System
Rapid response is critical when treating stroke, which occurs when a brain blood vessel is blocked by a clot or bursts. When brain cells don’t get oxygen, they can perish in minutes, says neurologist Dr. Steven Cramer, who established the UC Irvine Health Comprehensive Stroke & Cerebrovascular Center, one of the nation’s first. “It’s what I call a FedEx nightmare,” he says. “You have 100 billion customers – the cells – and if you’re two minutes late with the oxygen, they all die.”
UCI spearheaded the creation of a “spoke and hub” system: County policy now requires paramedics to take patients suffering stroke symptoms either to “hub” hospitals with neurovascular specialists available 24/7 or to “spoke” hospitals that can quickly transfer them to hubs if necessary.
Days Four and Five: Under Construction
A “greenie” – that’s what I call the attendants because of their scrubs – transforms one side of my bed into a wheelchair with the push of a few buttons and gives me a sponge bath. I’m dying to take a shower – my hair is still caked – but I’m terrified I’ll die if I do. A counselor told me my fear is normal, because the shower is where I had my stroke.
An occupational therapist named Gigi Oh introduces herself and attaches small devices to my left shin and wrist. They’re like Fitbits but lighter and better equipped to monitor medical recovery. She tells me they’ll track how often I move my hand and leg. She sets a timer to remind me with a little ping to periodically attempt to move my limbs – and sets target numbers. I try as hard as I can to move anything on my left side. I think I feel something, but I’m not sure. The devices register zero.
She downloads an app on my phone that shows me my chances for recovery, based on a database of thousands of patients who have undergone similar treatments. Eighty-three percent. For the first time, I feel hope.
Gigi interviews me about my goals – what I want to do when I get better. I tell her about our real estate business and that I need to use a computer. I tell her I’m the one who runs the house – cooking, cleaning, getting the kids to school and team practices.
“What do you like to do for you?” she asks.
I can’t think of anything. Finally I say, “Any kind of dance. I used to love to dance.”
As I drift off that night, the ping sounds. My left leg twitches.
Professor David Reinkensmeyer, a UCI biomedical engineer, visits early the next day. His lab and Cramer’s have worked together closely for years. He’s invented “robotic exoskeletons” – personalized robots for different body parts, such as my damaged arm and leg – that will respond to my healing brain’s intention to move and help me practice “the right moves” to restore gait, balance and strength. I’ll also use a game board and other tools.
My care team is designing a personalized program based on my genetic profile and the pattern of my brain damage. They’ve winnowed the database of stroke survivors to 20 with very similar profiles to mine who made major or total recoveries. By looking at everything from their diets and medications to the times of day that they exercised, my caregivers will aim to do the same for me.
In the future, stem cells, electronic drumming devices and other therapies could allow brains with blocked arteries to quickly open healthy alternate pathways, detouring around a stroke and preventing cerebral injury, paralysis, slurred speech and other impacts.
Investigators at UCI’s Sue & Bill Gross Stem Cell Research Center will soon test whether stem cells taken from our skin and bone marrow could be grown into healing agents. And Professor Ron Frostig’s team found that stroking the whiskers of rats with blocked brain arteries reversed ischemic strokes. Similar tactile stimuli at key body points could do the same in humans; clinical trials are expected by 2018.
Professor Reinkensmeyer hands me a cap that looks like a fishing net covered with hundreds of LED lights. It’s called a “geodesic sensor net.” It works for stroke patients like an EEG does for heart patients. It will allow the physicians and therapists to monitor how my brain is responding as I practice physical activities, showing when I have good focus and when I lose it. Maybe when the kids see me wearing this, they’ll laugh instead of looking so scared.
After Professor Reinkensmeyer leaves, Gigi wheels me down the hall to a physical therapy room. She attaches an exoskeleton to my left leg, then straps me into a soft harness tethered to a robot on the ceiling. It lifts me high, and I swing like a baby, my feet lightly touching the floor. It’s scary, but it feels good. The sling and brace will allow me to safely practice standing, balancing and walking. As I get better, the greenies will deliberately shake me so that my brain can better learn how to self-correct the variability caused by my stroke. None of it seems possible.
“As I get better, the greenies will deliberately shake me so that my brain can better learn how to self-correct the variability caused by my stroke.”
Two Weeks After Stroke
One of my best friends, Marika, visits. I’m so happy to see her. We joke about how we used to slay the boys in high school with our jazz routine. Sitting in my wheelchair, I tap my left leg up and down unconsciously. Joseph starts shouting. “Did you see that? She moved her leg! Marika, take a video with your phone!”
He demands I do it again – and I can!
Three to Eight Weeks After Stroke
I get pretty good at wheeling myself into the bathroom or down the hall with my right hand. Too good. Gigi rolls in a prototype wheelchair one day with long metal arm bars angled toward the ceiling. It’s based on a technology called LARA, for lever-actuated resonance assistance. “Try to move the wheelchair with both arms,” she says. I look at her like she’s crazy. She props my arms on each bar and helps me push down. The chair rolls forward. I use my right arm to prop my left arm back up, then attempt to push down with both again. It takes a few tries, but I can do it! I start crying. Gigi pretends not to notice.
I also play on a console with a computer screen. Instead of a keyboard, there are brightly colored buttons. Student researchers put a plastic mallet in my left hand and tell me to bang on the big red and green buttons. It helps restore gross motor functions. It feels pretty satisfying when I manage to hit one and see the computer screen light up with the points I’ve earned. Next the attendants tell me to turn a wheel in the center of the board with my fingers – fine motor coordination. I can’t do it. Just keep trying, they say. I do it for my kids.
I test out the video game Guitar Hero with the cool blue MusicGlove, invented by Professor Reinkensmeyer’s students, which responds to me pinching my fingers together or tapping them by making it look and sound as if I’m playing songs on the screen. My scores are pretty lousy at first, but I slowly start racking up points. My kids get a kick out of the games when they visit and like watching a YouTube video of old-time rapper Dr. Dre using a full-body exoskeleton that UCI invented. It’s got 3 billion views.
The hot water feels good, but I’m still scared. I never used to be scared of anything happening to me. It’s been one month since I fell.
Each day, I work hard to get out of bed, transfer to the toilet, move my arm and – toughest of all – walk. I thought it would be like learning to ride a bicycle again: easy. It’s not. I have to think about every step. Balance, right foot, left foot. I pray a lot more than I used to, for patience. It helps to see other patients recovering.
I practice “cooking” and “shopping.” With the exoskeleton on my left arm, I toggle computer keys to “lift” an egg on the video screen and crack it into a pan. I “lift” a block of wood, and on the screen it looks like I’m taking products from grocery store shelves and putting them into a shopping cart.
My brain is on fire. That’s what Dr. Cramer tells me. It’s renewing itself, growing new neurons and synapses. He can see it on the telerehabilitation monitors. Keep it up, Leticia, keep dancing. I tap my left foot as hard as I can every chance I get.
“My brain is on fire. That’s what Dr. Cramer tells me. It’s renewing itself, growing new neurons and synapses.”
“Are you ready for the holodeck, Captain?” Gigi says with a smile one day. We head to a room with big 3-D displays and patients wearing virtual reality goggles. Eddie has begged us to get him a set, but I’ve never tried them. She sets up a simulation to play virtual golf. Ha! I’ve never played in my life.
The robots help me to bend over to place the ball, balance and swing. I walk on a treadmill along a 3-D virtual course after hitting each ball. The greenies ask me to play a round with another patient. The system will handicap us to about the same level, so it will be a good match. I’m still a terrible golfer, even with help from robots. But I laugh while I’m trying, which feels good. I play nine holes and beat my partner by two strokes. I’m tired, but the time flew by.
Back in my room, Gigi tells me that she analyzed data from my golf session. I moved my leg in many directions, showed better balance reactions, and improved my hand movement. The weight shifting and other transitions are similar to cooking, she notes. She shows me my progress on my cellphone. I exceeded the target amount for today. Congrats!
Day 56: Christmas Eve
Dr. Cramer says I can go home. He’s reviewed the data from my brain and the robots. I’m medically stable, and my movement is strong enough that I can keep practicing there.
Gigi gives me two more devices – smaller exoskeletons made of metal and plastic and Velcro for my hand and leg. They’ll help me walk safely and use my fingers, but only as much as I need.
“They’ll keep turning themselves down as you get better, so don’t get used to them,” she says.
She tells me there’s a rehabilitation holodeck at my local 24-hour gym. With so many baby boomers experiencing disabilities and losing mobility, holodecks are also at YMCAs, community centers and other locations now.
“They’re not as high-tech as the hospital’s, but they’re still fun,” Gigi says. “And you can work out with some of the friends you’ve made through the UCI support network.”
She’ll be checking all my movement data.
“Don’t even think about becoming a couch potato,” she warns.
I’m so glad to be home. Sophia and I always put up the Christmas tree, and they waited for me. She whirls around the sweet-smelling branches so fast I’m worried she’s going to knock it over. I force myself to hang ornaments slowly, one after the other, using my hand exoskeleton. It beats video games any day.
Engineering Ways Forward
Transformative technologies already help people with paraplegia and other challenges regain mobility. Slings, braces, electronic implants and computer games are used in rehabilitation, and additional advances are in the works:
- UCI’s Brain Computer Interface Lab developed an implant for a man with spinal cord injury that enabled him to walk again last year – treatment that could aid stroke survivors too.
- Cognitive scientists and big data experts are setting up databases that cross-reference injuries, outcomes, DNA profiles and other information. It’s part of a major future trend: customized medicine.
- Video game theorists and psychologists specializing in motivation are developing mind-engaging products to keep people practicing critical repetitive movements and doing other restorative exercises.
- Lightweight robotic devices can be significant spurs to correct physical therapy. The ArmeoSpring arm brace, based on Professor David Reinkensmeyer’s engineering, is now used at 700 clinics and hospitals worldwide, and his LARA wheelchair lever prototype is being commercialized.
Months Three Through Six: Home
Joseph stretches my left side every morning. It hurts, but I know he has to do it. Then I spend three hours at my local holodeck relearning movements with help from my exoskeletons. I videoconference with Gigi twice a week and see her once a week at her office, where she adjusts my exercises and changes devices. I track on my phone whether I’m meeting my targets. The help from my exoskeletons is decreasing. I begin paying bills online. I never thought I’d be happy to do this!
Dr. Cramer calls. He wonders if I’d like to participate in a research study. I’d have a small sensor implanted under my skin to measure sweat, sugar levels, heart rate and other factors to detect future health problems. I might also be asked to wear a necklace or bracelet to measure things. It could help us know very quickly if I’m at risk for another stroke, diabetes or other problems. He says that in the near future everyone may be “microchipped” – and grateful for it.
“Sign me up,” I say.
Day 180: Stepping Out
Gigi says it’s time to get rid of the exoskeletons. I can move well enough without them. I feel somewhat uncoordinated, but free.
I tell her I saw a story online about Parkinson’s disease patients learning to dance. I want to try it. She says I should contact iMove at UCI. Kelli Sharp, a biologist and assistant professor of dance science, emails a few hours later with a schedule of dance classes for recovering stroke survivors in Riverside and Orange counties. She says they’re highly effective for people with chronic brain injuries. Twenty years ago, she and another UCI dance professor began working with kids with cerebral palsy. Their techniques were proven to restore mobility and reduce anxiety. Ballet or tap might be tough, but I’m an ideal candidate for ballroom dancing. Joseph can be my partner.
“I’ll always be your partner,” he says. “Just don’t move too fast.”
Dancing Back to Health
Assistant professor of dance science Kelli Sharp – who first studied regenerative spinal cord function, then earned a doctorate in physical therapy – researches how to help ballerinas extend their careers, using the brain to strengthen connections in neuromuscular systems. She also utilizes dance to explore how to help people with neurological disorders both emotionally and physically.
“So they’re up, they’re moving, and functional MRIs and other work shows the pathways in their brains are changing. They’re regaining function, and they’re experiencing great satisfaction,” she says.
Sharp works with other UCI researchers to track molecular changes in patients’ brains as they do exercises to improve everything from hindquarter strength to perceiving where their hand is in space as it holds a cellphone.
Anatomy & neurobiology professor David Reinkensmeyer contributed to this report. While this story is about a hypothetical patient in the future, it includes the experiences of Maria Ortiz and her family with their permission.