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

Why Does Your Body Twitch As You're Falling Asleep?

If you’ve ever found yourself drifting off to sleep only to be woken by a vigorous, full-body twitch or jerk, then do not feel alarmed. You’re among the estimated 60 - 70 % of Americans who regularly experience a phenomenon known as a hypnic jerk—also known as a hypnagogic jerk, or sleep start—which strikes as a person falls into a deep sleep. Here’s what to know about it.

What do sleep jerks feel like?

Hypnic jerks—involuntary twitches or jolts which occur during the night—can affect people in different ways. Many people will sleep right through them, but for others, they are vigorous enough to wake them up.

Although there is no definite explanation for what causes hypnic jerks, people are more likely to suffer from them when they’re sleep deprived or anxious, or when they do sleep-impairing habits before going to bed, like drinking caffeine or doing exercise close to bedtime, says James Wilson, a U.K.-based sleep behavior and sleep environment expert. “For people who suffer from hypnic jerks, it’s awful,” he adds. “They worry about it before they go to bed, which makes it worse.”

Jacqui Paterson, who is 44 and lives in the U.K., says she has experienced these kinds of twitches on an almost-nightly basis for about three years.

“When I was about 41, I started getting insomnia, which I’d never had in my life before,” she says. “Initially, I was staying awake all night, but I now get these annoying jerks which wake me up exactly an hour after I fall asleep, like someone has set an alarm in my head. I seem to have replaced one evil with another.”

Paterson says the jerks come more regularly when she feels concerned or preoccupied. If she worries about them happening before she goes to bed, then it “almost guarantees” that she will suffer from them that night.

The jerks feel like a jolt or an electric shock, Paterson says. “I’ve heard people talk about getting a falling sensation when they drop off to sleep,” she says. “To me, the feeling is like that but on steroids. It’s like someone has come and slapped me. It’s a really shocking feeling, like jumping into freezing cold water. I always wake up feeling totally alert.”

What causes hypnic jerks?

Put simply, hypnic jerks are caused when one part of the brain tries to go to sleep more quickly than other parts of the brain.

“The complexity of going to sleep and waking up is incredible, and sometimes—particularly when we are sleep deprived—our brain doesn’t shut down normally, which means we get this sort of jerking movement when we’re in a light sleep,” says Wilson. Often, he adds, the brain tries to make sense of it, “which is when we imagine ourselves falling off the sidewalk, a cliff or in a hole.”

The reason why some people experience the twitches at such a predictable time is due to their circadian rhythm, or body clock, Wilson says. “Normally when we go to sleep, about half an hour later we go into a deep stage of sleep during which we wouldn’t get these hypnic jerks,” he says. “If someone is sleep deprived, as they go through the process of falling asleep, the brain will get stuck at the same point in time. Usually if we can help people address their sleep deprivation, the instances decrease or disappear altogether.”

How can you prevent sleep jerks from happening?

There are ways to limit the effects, particularly by making a conscious effort to sleep better. “Try and get in a good routine around sleep,” Wilson says. “Wake up at the same time every day, and wind down properly before going to bed, making sure the activities you do in the hour before going to sleep are relaxing to you. Like most issues surrounding sleep, preventing hypnic jerks is all about trying to solve that sleep deprivation.”

Wilson also suggests that if a person suffers from them at the same time every night, they could ask a housemate or family member to disturb their sleep about five minutes before the jerks tend to occur, either by encouraging them to turn over in bed or rustling something near them. Often, that will help stop the twitches from happening, he says.

This article originally appeared on time.com and was written by Kate Samuelson

Stress: It’s Not in Your Head, it’s in Your Nervous System

Traumatic Memory and How to Heal it

Have you ever been told when you’re stressed to stop worrying and just relax? That it’s all in your head? It would be nice if it were that simple. But it’s not.

Physiology research shows that the stress response memory lives in your nervous system. Take for example exposure to a stressful event. One in which you felt helpless, hopeless, and lacked control. In this case your autonomic nervous system (ANS) is engaged. This is the part of the nervous system responsible for controlling unconscious bodily actions like breathing. To be more specific, it was the sympathetic branch (fight or flight) of the ANS that kicked in while you were strained. In addition, the hypothalamic-pituitary-adrenal axis of the midbrain began firing. In which a signal from your hypothalamus sends a hormonal message to your pituitary gland that stimulates to your adrenal glands.

To activate this fight or flight response, stress hormones like cortisol and adrenaline are released from your adrenal glands. They help our body suddenly mobilize to flee danger. According to Peter A. Levine, trauma expert in the field of psychotherapy, trauma occurs when this biological process is overwhelmed and a person is unable to release and process the stressful event. It is possible to avoid a traumatic response by discharging the energy generated. For example, shaking, crying, and screaming can allow the individual to physically process the stress.

Stress is not all in your head.

However, if the stress response is not processed, it remains in the tissues of the body. When a subsequent stressful event that does not pose a serious threat occurs, the traumatic memory is recalled. A large amount of stress hormones are released. Blood rushes to extremities, pupils dilate, muscle tone increases presenting as tension, breathing rate increases, the heartbeats faster, and sweating occurs. Hence, the nervous system responds as if this small incident is life threatening.

This biological response is clearly beyond the ability to rationally control. You can’t think your way out of it. Chronic stress leads to dissociation or immobility, a state of sympathetic charge and hormonal release, which is health damaging. The brainstem (the primitive part of the brain) governs emotional experience and biological response. When the brainstem is activated by the fight or flight response, it trumps the more developed front of the brain, the prefrontal cortex. It is therefore not possible to be in the primitive state of fight or flight and also to think rationally and critically (as the prefrontal cortex would have us do).

Levine elaborates:

The question is: how can humans become unstuck from immobility? Moving out of this frozen state can be a fiercely energetic experience. Without a rational brain animals don’t give it a second thought, they just do it. When humans begin to move out of the immobility response, however, we are often frightened by the intensity of our own energy and latent aggression, and we brace ourselves against the power of the sensations. This bracing prevents complete discharge of energy necessary to restore normal functioning.

Unprocessed stress is stored in the body as traumatic memory.

Unprocessed stress becomes traumatic memory that lies dormant in the body. A present day trigger can cause the stored memory to resurface. Understanding what is happening inside our body and brain, gives us compassion. Learning why our body responds the way it does, leads to awareness and empowerment. It moves us out of being isolated, fearful, victims. By caring for our bodies and understanding their self-protective responses, we can release shame.

When we comprehend the physiologic process that is trying to keep us safe, from an old memory or trauma, we can replace inner judgement with kindness. Self-love becomes possible. It may not be serving us in the present but in the past it did. In fact, this same response helped us survive.

The work is then to re-train the body. This can be done by invoking practices such as felt sense oriented meditation, deep breathing, vocal toning, spontaneous movement and dance, yoga, listening to soothing music, spending time in nature, running, or hiking. Or simply receiving a hug from a loved one, which releases oxytocin, a natural hormone produced by the pituitary gland that promotes bonding and connection.

Practices such as yoga and time in nature help to release stored trauma. 

These are tools to deactivate the sympathetic response and activate the opposing parasympathetic response, called the rest and digest mechanism. The goal is to feel safe. To regulate breathing, slow the heartbeat, and circulate blood back to the vital organs

These powerful practices change our physiology and affect our mood. The next time someone suggests it’s all in your head, you will have a different response. This knowledge empowers us to heal past wounds. Through acknowledging the power trauma plays in your life and understanding the mechanisms by which healing occurs, you can create a more embodied, joyful life.

This article originally appeared on upliftconnect.com and was written by Melody Walford.

Does Acupuncture Work by Re-Mapping The Brain?

Acupuncture is a form of traditional medical therapy that originated in China several thousand years ago. It was developed at a time bereft of tools such as genetic testing or even a modern understanding of anatomy, so medical philosophers did the best they could with what was available – herbs, animal products and rudimentary needles. In the process, perhaps, they stumbled on an effective medical approach.

In the past century, some modernisation has taken place. For instance, acupuncture has been paired with electrical currents, allowing for stimulation to be more continuous and to penetrate deeper into the body. This approach was termed electro-acupuncture and represents a convergence between the ancient practice of acupuncture therapy and modern forays into targeted electrostimulation delivered to the skin or nerves. Such approaches have attracted the attention of the pharmaceutical industry and are part of a growing class of neuromodulatory therapies.

So why all the rancour against acupuncture from some corners of the internet (and academia)? Shouldn’t we apply our modern research methods to see which classical acupuncture techniques have solid physiological backing?

It’s not as easy as it seems. Let’s look at the clinical research. A recent landmark meta-analysis threw together data from thousands of chronic-pain patients enrolled in prior clinical trials, finding that acupuncture might be just marginally better than sham acupuncture (in which non-inserted needles are used as a placebo control). The differences were statistically significant, but lack of a larger difference could be due to the clinical outcome measure that the researchers studied. Symptoms such as pain (along with fatigue, nausea and itch) are notoriously difficult for different people to rate in a consistent manner. Conventional wisdom says that these kinds of symptoms are improved by placebo, but what about improvements in the body’s physiology? For instance, in a recent study that assigned an albuterol inhaler for asthma to some patients and sham acupuncture to others, patients reported both as effective. But objective physiological measures demonstrated significant improvement only for albuterol. It’s clear that in evaluations of acupuncture, research should explicitly hunt for potential physiological improvements, in addition to patient reports.

While most chronic-pain disorders lack such established, objective outcomes of disease, this is not true for carpal tunnel syndrome (CTS), a neuropathic pain disorder that can be validated by measuring electrical conduction across the median nerve, which passes through the wrist. Interestingly, the slowing of nerve conduction at the wrist does not occur in isolation – it’s not just the nerve in the wrist that’s affected in CTS. My own department’s research and others’ has clearly demonstrated that the brain, and particularly a part of the brain called the primary somatosensory cortex (S1), is re-mapped by CTS. Specifically, in functional magnetic resonance imaging (fMRI) brain scans, the representation of fingers innervated by the median nerve are blurred in S1. We then showed that both real and placebo acupuncture improved CTS symptoms. Does this mean that acupuncture is a placebo? Maybe not. While symptom relief was the same immediately following therapy, real acupuncture was linked to long-term improvement while sham acupuncture was not. And better S1 re-mapping immediately following therapy was linked with better long-term symptom reduction. Thus, sham acupuncture might work through an alternative route, by modulating known placebo circuitry in the brain, while real acupuncture rewires brain regions such as S1, along with modulating local blood flow to the median nerve in the wrist.

Where you stick the needle might matter as well. While site-specificity is one of the key features of acupuncture therapy, it has been controversial. Interestingly, in the S1 region of the brain, different body areas are represented in different spatial areas – this is how we localise the mosquito that’s biting us, and swat it. Different S1 areas might also pass along information to a diverse set of other areas that affect different bodily systems such as the immune, autonomic and other internal motor systems. As far as acupuncture is concerned, the body-specific map in S1 could serve as the basis for a crude form of point specificity. In our study, we compared patients receiving real acupuncture locally to the wrist with patients receiving real acupuncture far from the wrist, in the opposite ankle. Our results suggested that both local and distal acupuncture improved median nerve function at the wrist. This suggests that the brain changes resulting from acupuncture might not just be a reflection of changes at the wrist, but could also drive the improved median nerve function directly by linking to autonomic brain regions that control blood vessel diameter and blood flow to the median nerve.

This new research clearly demonstrates that bodily response is not the only means by which acupuncture works; response within the brain might be the most critical part. Once we better understand how acupuncture works to relieve pain, we can optimise this therapy to provide effective, non-pharmacological care for many more chronic-pain patients.

This article originally appeared on Aeon & written by Vitaly Napadow.