A Neurosurgeon’s Remarkable Plan to Treat Stroke Victims With Stem Cells

Gary Steinberg defied convention when he began implanting living cells inside the brains of patients who had suffered from a stroke.

The day she had a stroke, Sonia Olea Coontz, a 31-year-old from Long Beach, California, was getting ready to start a new career as a dog trainer. She had just wrapped up a week of training, and she and her boyfriend were taking their own dogs to the park. But something strange kept happening: She’d try to say one thing and end up saying another.

By evening, her boyfriend was worriedly telling her that the right side of her face had gone slack. She wasn’t able to focus on anything except the bedroom walls, and she wondered how they’d gotten to be so white. “It was very surreal,” she recalls.

Coontz spent the next six months mostly asleep. One day she attempted to move an arm, but she couldn’t. Then a leg, but she couldn’t move that, either. She tried to call for her boyfriend but couldn’t say his name. “I am trapped in this body,” she remembers thinking.

That was May 2011. Over the next two years, Coontz made only small improvements. She developed a 20-word spoken vocabulary and could walk for five minutes before needing a wheelchair. She could move her right arm and leg only a few inches, and her right shoulder was in constant pain. So when she learned about a clinical trial of a new treatment at Stanford University School of Medicine, she wasn’t fazed that it would involve drilling through her skull.

At Stanford, a magnetic resonance scan showed damage to the left half of Coontz’s brain, an area that controls language and the right side of the body. Ischemic strokes, like Coontz’s, happen when a clot blocks an artery carrying blood into the brain. (Rarer, but more deadly, hemorrhagic strokes are the result of weakened blood vessels that rupture in the brain.) Of the approximately 800,000 Americans who have strokes each year, the majority make their most significant recoveries within six months. After that, their disabilities are expected to be permanent.

On the day of Coontz’s procedure, Gary Steinberg, the chair of neurosurgery, drilled a nickel-size burr hole into Coontz’s skull and injected stem cells around the affected part of her brain. Then everyone waited. But not for long.

Coontz remembers waking up a few hours later with an excruciating headache. After meds had calmed the pain, someone asked her to move her arm. Instead of moving it inches, she raised it over her head.

“I just started crying,” she recalls. She tried her leg, and discovered she was able to lift and hold it up. “I felt like everything was dead: my arm my leg, my brain,” she says. “And I feel like it just woke up.”    

Coontz is part of a small group of stroke patients who have undergone the experimental stem cell treatment pioneered by Steinberg. Conventional wisdom has long maintained that brain circuits damaged by stroke are dead. But Steinberg was among a small cadre of researchers who believed they might be dormant instead, and that stem cells could nudge them awake. The results of his trial, published in June 2016, indicate that he may well be right.

“This important study is one of the first suggesting that stem cell administration into the brain can promote lasting neurological recovery when given months to years after stroke onset,” says Seth Finklestein, a Harvard neurologist and stroke specialist at Massachusetts General Hospital. “What’s interesting is that the cells themselves survived for only a short period of time after implantation, indicating that they released growth factors or otherwise permanently changed neural circuitry in the post-stroke brain.”

Steinberg, a native of New York City, spent his early career frustrated by the dearth of stroke therapies. He recalls doing a neurology rotation in the 1970s, working with a woman who was paralyzed on one side and couldn’t speak. “We pinpointed exactly where in the brain her stroke was,” Steinberg says. But when Steinberg asked how to treat her, the attending neurologist replied, “Unfortunately, there’s no treatment.” For Steinberg, “no treatment” was not good enough.

After earning his MD/PhD from Stanford in 1980, Steinberg rose to become the chair of the school’s neurosurgery department. In 1992, he co-founded the Stanford Stroke Center with two colleagues.

In the years that followed, two treatments emerged for acute stroke patients. Tissue plasminogen activator, or tPA, was approved by the FDA in 1996. Delivered by catheter into the arm, it could dissolve clots, but it needed to be administered within a few hours of the stroke and caused hemorrhaging in up to 6 percent of patients. Mechanical thrombectomy emerged about a decade later: By inserting a catheter into an artery in the groin and snaking it into the brain, doctors could break up a clot with a fluid jet or a tiny suction cup. But that treatment could only be delivered within six hours of a stroke and couldn’t be used in every case. After the window closed, doctors could offer nothing but physical therapy.

When Steinberg started looking into stem cell therapy for stroke patients, in the early 2000s, the idea was still unorthodox. Stem cells start off unspecialized, but as they divide, they can grow into particular cell types. That makes them compelling to researchers who want to create, for example, new insulin-producing cells for diabetics. But stem cells also help our bodies repair themselves, even in adulthood. “And that’s the power that Steinberg is trying to harness,” says Dileep Yavagal, a professor of clinical neurology and neurosurgery at the University of Miami.

Steinberg began testing this in a small trial that ran between 2011 and 2013. Eighteen volunteers at Stanford and the University of Pittsburgh Medical Center agreed to have the cells—derived from donor bone marrow and cultured by the Bay Area company SanBio—injected into their brains.

Sitting in his office, Steinberg boots up footage of a woman in her 70s wearing a NASA sweatshirt and struggling to wiggle her fingers. “She’s been paralyzed for two years. All she can do with her hand, her arm, is move her thumb,” says Steinberg. “And here she is—this is one day later,” he continues. Onscreen, the woman now touches her fingers to her nose. “Paralyzed for two years!” Steinberg repeats jubilantly.

His staff calls this woman and Coontz their “miracle patients.” The others improved more slowly. For example, a year after their surgery, half of the people who participated in a follow-up exam gained 10 or more points on a 100-point assessment of motor function. Ten points is a meaningful improvement, says Steinberg: “That signifies that it changes the patient’s life.” His team hadn’t expected this. “It changes the whole notion—our whole dogma—of what happens after a stroke,” he says.

But how did the stem cells jump-start those dormant circuits? “If we understood exactly what happened,” he says wryly, “we’d really have something.” Here’s what didn’t happen: The stem cells didn’t turn into new neurons. In fact, they died off within a month.

Steinberg thinks the circuits in question were somehow being inhibited. He’s not exactly sure why, but he thinks chronic inflammation could be one reason. He has a clue: After the procedure, 13 of his patients had temporary lesions in their brains. Steinberg thinks these indicated a helpful immune response. In fact, the size of the lesions after one week was the most significant predictor of how much a patient would recover.

For all 18 patients, Steinberg also thinks the cells secreted dozens, perhaps hundreds, of proteins. Acting in concert, these proteins influenced the neurons’ environment. “Somehow,” Steinberg reflects, “it’s saying, ‘You can act like you used to act.’”

Some of the participants had adverse reactions to the surgery, but not to the cells themselves. (A small European study published later also indicated that stem cells are safe for stroke sufferers.) And Steinberg says his patients’ recovery “was still sustained on all scales at two years.”

He’s now collaborating with Yavagal on a randomized controlled study that will include 156 stroke patients. Key questions await future researchers: How many cells should doctors use? What’s the best way to administer them? And are the cells doing all the work, or is the needle itself contributing? Could the death of the cells be playing a role?

Steinberg thinks stem cell therapy might help alleviate Parkinson’s, Lou Gehrig’s disease, maybe even Alzheimer’s. His lab is also testing its effects on traumatic brain and spinal cord injuries. Even though these conditions spring from different origins, he thinks they might all involve dormant circuits that can be reactivated. “Whether you do it with stem cells, whether you do it with optogenetics, whether you do it with an electrode, that’s going to be the future for treating neurologic diseases.”

Six years after her stroke, Coontz now speaks freely, although her now-husband sometimes has to help her find words. Her shoulder pain is gone. She goes to the gym, washes dishes with both hands and takes her infant son on walks in the stroller. For Coontz, motherhood is one of the greatest joys of post-stroke life. During her pregnancy, she worked out five times a week so she would be able to hold and bathe and deliver the baby. After so many medical procedures she couldn’t control, this time, she felt, “I am awake, I can see, I know how I want this to be.”

Her son is now 1 year old. “My husband picks him up and holds him way over his head, and obviously I can’t do that,” she says. “But I will. I don’t know when, but I will. I guarantee it.”

This article originally appeared on smithsonianmag.com and was written by Kara Platoni

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It's Official: Yoga Helps Depression

Evidence keeps stacking up that yoga is a boon for both physical and mental health conditions. Now, a small new study from Boston University finds that taking yoga classes twice a week may help ease depression, thanks in part to deep breathing.

The study, which was published in the Journal of Alternative and Complementary Medicine, included 30 people from ages 18 to 64 with clinical depression, who either were not taking antidepressants or had been on a steady dose for at least three months. Half of the participants were assigned to take a 90-minute Iyengar yoga class three times per week, as well as four 30-minute sessions at home each week. People in the other group took two group classes and three at-home sessions every week.

Iyengar yoga classes emphasize alignment, precise postures and controlled breathing. The classes taught in the study also included 20 minutes of slow, gentle breathing, at a rate of five inhales exhales through the nose per minute.

After about three months, most of the people in both groups had lowered their scores on a depression-screening questionnaire by at least 50%. Not surprisingly, more yoga was better; those who took three classes per week had lower depression scores than those who took two per week.

But since many participants mentioned that the larger time commitment was challenging, the researchers actually recommend two classes per week, saying that the regimen still comes with meaningful benefits.

That yoga seems to be effective is good news for people struggling with depression. Lead author Dr. Chris Streeter, associate professor of psychiatry and neurology at Boston University School of Medicine, says that the practice has far fewer side effects and potential drug interactions than mood-altering medications. The most common complaint reported in the study was a small one—temporary muscle soreness—and one participant experienced distressing thoughts while practicing breathing exercises at home.

Some people who haven’t responded to traditional treatments might do well with yoga, because unlike antidepressant drugs, yoga and deep breathing target the autonomic nervous system, Streeter says. “If your autonomic nervous system is balanced out, then the rest of the brain works better,” she says. Research shows that 40% of people on antidepressants do not recover fully from depression, says Streeter, which puts them at increased risk for a relapse. “Getting that 40% all the way better is a really important goal. Instead of adding another drug, I would argue that yoga is another thing you can add to the treatment regimen that might help.”

More research is needed to determine how yoga stacks up against other treatments. (A larger trial comparing yoga to walking is underway, the study notes.)

While Iyengar yoga is generally considered to be a safe practice for people of all levels, it’s not the only type with health benefits, Streeter adds. “It depends on who the person is and what they’re looking for,” she says. For now, what’s clear is that the type with the most health benefits will be whichever kind you stick with.

This article originally appeared on time.com and was written by AMANDA MACMILLAN.

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What is Pain and What is Happening When We feel It?

What is pain? It might seem like an easy question. The answer, however, depends on who you ask.

Pain doesn’t originate at the site as most think, it’s created by the brain so we protect the area that’s in danger.

Some say pain is a warning signal that something is damaged, but what about pain-free major trauma? Some say pain is the body’s way of telling you something is wrong, but what about phantom limb pain, where the painful body part is not even there?

Pain scientists are reasonably agreed that pain is an unpleasant feeling in our body that makes us want to stop and change our behaviour. We no longer think of pain as a measure of tissue damage – it doesn’t actually work that way even in highly controlled experiments. We now think of pain as a complex and highly sophisticated protective mechanism.

How does pain work?

Our body contains specialised nerves that detect potentially dangerous changes in temperature, chemical balance or pressure. These “danger detectors” (or “nociceptors”) send alerts to the brain, but they cannot send pain to the brain because all pain is made by the brain.

When you’re injured, the brain makes an educated guess which part of the body is in danger and produces the pain there.

Pain is not actually coming from the wrist you broke, or the ankle you sprained. Pain is the result of the brain evaluating information, including danger data from the danger detection system, cognitive data such as expectations, previous exposure, cultural and social norms and beliefs, and other sensory data such as what you see, hear and otherwise sense.

The brain produces pain. Where in the body the brain produces the pain is a “best guess scenario”, based on all the incoming data and stored information. Usually the brain gets it right, but sometimes it doesn’t. An example is referred pain in your leg when it is your back that might need the protecting.

It is pain that tells us not to do things – for example, not to lift with an injured hand, or not to walk with an injured foot. It is pain, too, that tells us to do things – see a physio, visit a GP, sit still and rest.

We now know that pain can be “turned on” or “turned up” by anything that provides the brain with credible evidence that the body is in danger and needs protecting.

All in your head?

So is pain all about the brain and not at all about the body? No, these “danger detectors” are distributed across almost all of our body tissues and act as the eyes of the brain.

When there is a sudden change in tissue environment – for example, it heats up, gets acidic (cyclists, imagine the lactic acid burn at the end of a sprint), is squashed, squeezed, pulled or pinched – these danger detectors are our first line of defence.

They alert the brain and mobilise inflammatory mechanisms that increase blood flow and cause the release of healing molecules from nearby tissue, thus triggering the repair process.

Local anaesthetic renders these danger detectors useless, so danger messages are not triggered. As such, we can be pain-free despite major tissue trauma, such as being cut into for an operation.

Just because pain comes from the brain, it doesn’t mean it’s all in your head. 

Inflammation, on the other hand, renders these danger detectors more sensitive, so they respond to situations that are not actually dangerous. For example, when you move an inflamed joint, it hurts a long way before the tissues of the joint are actually stressed.

Danger messages travel to the brain and are highly processed along the way, with the brain itself taking part in the processing. The danger transmission neurones that run up the spinal cord to the brain are under real-time control from the brain, increasing and decreasing their sensitivity according to what the brain suggests would be helpful.

So, if the brain’s evaluation of all available information leads it to conclude that things are truly dangerous, then the danger transmission system becomes more sensitive (called descending facilitation). If the brain concludes things are not truly dangerous, then the danger transmission system becomes less sensitive (called descending inhibition).

Danger evaluation in the brain is mindbogglingly complex. Many brain regions are involved, some more commonly that others, but the exact mix of brain regions varies between individuals and, in fact, between moments within individuals.

To understand how pain emerges into consciousness requires us to understand how consciousness itself emerges, and that is proving to be very tricky.

To understand how pain works in real-life people with real-life pain, we can apply a reasonably easy principle: any credible evidence that the body is in danger and protective behaviour would be helpful will increase the likelihood and intensity of pain. Any credible evidence that the body is safe will decrease the likelihood and intensity of pain. It is as simple and as difficult as that.

Implications

To reduce pain, we need to reduce credible evidence of danger and increase credible evidence of safety. Danger detectors can be turned off by local anaesthetic, and we can also stimulate the body’s own danger-reduction pathways and mechanisms. This can be done by anything that is associated with safety – most obviously accurate understanding of how pain really works, exercise, active coping strategies, safe people and places.

A very effective way to reduce pain is to make something else seem more important to the brain – this is called distraction. Only being unconscious or dead provide greater pain relief than distraction.

In chronic pain the sensitivity of the hardware (the biological structures) increases so the relationship between pain and the true need for protection becomes distorted: we become over-protected by pain.

This is one significant reason there is no quick fix for nearly all persistent pains. Recovery requires a journey of patience, persistence, courage and good coaching. The best interventions focus on slowly training our body and brain to be less protective.

This article was originally posted on https://theconversation.com/explainer-what-is-pain-and-what-is-happening-when-we-feel-it-49040

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