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

Video: Understanding Different Types of Back Pain

Are you having trouble treating your back pain? This video explains why back pain can be so difficult to diagnose and treat.

When you learn about your body, you are in control of how to support it well & correctly.

Click the photo to watch a short educational video!

Migraines: Preventative Care with Acupuncture

Acupuncture is the technique of piercing the body with a solid needle for therapeutic purposes. Acupuncture was developed in China and the first textbook describing the use of acupuncture is thought to date back to about 200BC. Western interest in acupuncture grew in the 1970’s with President Nixon’s visit to China and has steadily increased since then. The majority of acupuncture treatment in the UK is provided in private practice by professional (lay) acupuncturists who are not from an orthodox medical background. However, acupuncture is provided in almost all NHS pain clinics and by increasing numbers of GPs and physiotherapists.

Types of acupuncture

Two main philosophical approaches are usually recognised. Traditional Chinese medical concepts describe illness and disease as a disturbance of qi (a form of energy or ‘vital force’) within the body. Qi is said to flow along fourteen meridians on the body surface on which the acupuncture points are situated (rather like stations on the lines of the London Underground map). Acupuncture aims to re-establish the correct flow of qi throughout the meridians. Diagnosis may include detailed examination of the pulse and tongue. Needle placement is individualised, so each patient with migraine might receive a different number and distribution of needles. This is often combined with dietary advice and Chinese herbal treatment.

Western medical acupuncture is a modern scientific approach which is based on the biological effects of needling and on clinical and laboratory research. Acupuncture has been found to have effects on the nervous system, including locally where the needles are placed, in the spinal cord and brainstem, where a ‘damping effect’ occurs on pain transmission, and in areas of the brain which regulate the emotional aspects of pain. This may explain beneficial effects from ‘distant’ acupuncture points of traditional practice. Western medical acupuncture uses both local points (for instance on the head and neck) and distant points (such as hands and feet). A related approach is ‘trigger point’ acupuncture, in which tender points in muscles are needled to release muscle spasm contributing to the condition, for example in the neck and scalp.

Evidence for acupuncture

A major problem in acupuncture research is that most clinical trials in headache are ‘randomised, double-blind placebo-controlled trials’, which means that the treatment (typically a drug) is compared with a ‘placebo’ or dummy tablet of identical appearance so that neither the patients nor the researchers know which is which. This is done to minimise treatment expectations affecting the outcome. However, it is much more difficult to devise a ‘placebo’ acupuncture technique with which patients and researchers can be ‘blinded’. One method is called ‘sham’ acupuncture, in which the needles are inserted less deeply into the skin and away from classic acupuncture points. This relies upon the patient not knowing where the true points are and works best in those who have never had acupuncture before. The second method is to use a special needle held in a sheath, which hides it from the patient. The needle can then be made to enter the skin as usual, or to ‘prick’ the skin but not penetrate it (placebo). This has been shown to mimic the sensation of acupuncture effectively. There is much controversy about whether either of these methods are truly inactive like a drug placebo or may have specific effects because they stimulate nerve fibres lying under the skin. The other issue is that practitioners can never be ‘blinded’; they always know which treatment they are giving. For this reason the results of treatment must be assessed by another researcher unaware of which patients got which treatment, or by the patients themselves.

Acupuncture studies in headache have concentrated almost entirely on the prevention of headache rather than acute treatment. A Cochrane systematic review first published in 2001 analysed 16 studies involving 1151 patients and concluded that ‘the existing evidence supports the value of acupuncture for the treatment of idiopathic headaches’, but called for further large-scale studies. Large, randomised controlled clinical trials involving several thousand patients have now been conducted, funded by German health insurance companies. These studies have compared acupuncture with standard treatment (drugs and advice given by physicians) and demonstrate persistent and clinically relevant benefits under real-life conditions and equivalence to specialist drug management. However, no convincing evidence of superiority to ‘sham’ acupuncture has been shown for headache. To skeptics, this suggests that ‘acupuncture doesn’t work’ (i.e. ‘it is no better than placebo’). To supporters of acupuncture, it suggests that while the studies show that it may not matter quite so much how the acupuncture is done, i.e. where the needles are placed or how deeply, acupuncture is much better than no treatment and equivalent to conventional treatment options, with considerably fewer side-effects.

In so-called ‘pragmatic’ studies, the real-world effectiveness of acupuncture has been assessed when given in addition to usual treatment. Patients are randomized to ‘acupuncture’ or ‘no additional treatment (standard GP management) without the use of a placebo. In one such study, patients suffering with chronic headache (80% with migraine) were given 12 sessions of acupuncture over 3 months. This resulted in 34% fewer headache days, 15% less medication, 15% fewer days off work and 25% fewer GP visits after one year. The cost-effectiveness, expressed per ‘quality-adjusted life year’ (QALY), the recommended measure, was £9000 per QALY, well under the threshold of £20-30 000 per QALY) required by the National Institute of Clinical Effectiveness (NICE). These results have been repeated in Europe.

The National Institute for Health and Care Excellence (NICE) include in their headache guideline(2012, updated 2015) that a course of up to 10 sessions of acupuncture may be offered by a healthcare professional if neither topiramate or propranolol are suitable or work well for a particular patient. However, there is no mandate for health professionals to prescribe acupuncture. In practice its availability on the NHS is inconsistent.

Safety of acupuncture

Acupuncture is extremely safe if delivered by adequately trained practitioners. The most frequent side-effects are mild and include: minor bruising or bleeding, usually on needle withdrawal (3%), worsening of existing symptoms (1%) which usually lasts no more than two days and is sometimes associated with a good overall outcome; drowsiness, relaxation, or euphoria (3%) which is often experienced as pleasurable (and if so is not an adverse event!), and pain at the needling site (1%). Severe, extremely rare side-effects include a puncture lung or heart membrane (this is avoided by correct technique); transmission of blood-borne diseases (e.g. hepatitis C), avoided by using single-use, sterile, disposable needles, and skin infection (which is possible with ear acupuncture, particularly if indwelling studs are used).

Acupuncture at the Royal London Homeopathic Hospital

The Royal London Homeopathic Hospital, part of University College Hospital NHS Trust, introduced acupuncture into the NHS in 1977. It is the largest provider of acupuncture services to NHS patients, providing several thousand patient sessions per year. All treatment is provided by conventionally qualified doctors, nurses and physiotherapists who are additionally trained in acupuncture.  Both Western and traditional Chinese techniques are used. With increasing scientific evidence for the effectiveness of acupuncture, the RLHH has concentrated on the challenge of providing NHS acupuncture on the scale and frequency required to treat the large number of sufferers with chronic painful conditions including headache and migraine, facial pain, back and neck pain and knee osteoarthritis. It has set up a number of pioneering group treatment services, where patients are treated up to six at a time initially on a weekly or two-weekly basis, followed by monthly maintenance treatment for those who respond. Clinical audit has demonstrated that the results compare with those from clinical trials.

References

• Linde K et al. Acupuncture for migraine prophylaxis. Cochrane Database of Systematic Reviews 2009, Issue 1. Art. No.: CD001218.

• Diener HC. et al. Efficacy of acupuncture for the prophylaxis of migraine: a multicentre randomised controlled clinical trial. Lancet Neurol. 2006 Apr;5(4):310-6.

• Linde K, Streng A, Jurgens S, Hoppe A, Brinkhaus B, Witt C et al. Acupuncture for patients with migraine: a randomized controlled trial. JAMA 2005;293(17):2118-25.

• Vickers A. et al. Acupuncture for chronic headache in primary care: large, pragmatic, randomised trial BMJ 2004;328;744-9.

• Wonderling D et al. Cost effectiveness analysis of a randomised trial of acupuncture for chronic headache in primary care. BMJ 2004;328;747.

• National Institute for Health and Care Excellence.  Headaches in over 12s: diagnosis and management (NICE guidelines [CG 150]).  2012 (updated 2015).

this article originally appeared on migrainetrust.org, with contribution by Dr Saul Berkovitz MRCP

How Does Yoga Relieve Chronic Pain?

Chronic pain triggers changes in brain structure that are linked to depression, anxiety, and impaired cognitive function. New research shows that practicing yoga has the opposite effect on the brain and can relieve chronic pain.

Chronic pain alters brain structure. Brain imaging studies have shown that chronic pain leads to changes in gray matter volume and the integrity of white matter connectivity. Gray matter is home to the neurons in specific brain regions, while white matter creates communication lines between your various brain regions.

In a recent lecture, “Effect of Environment on the Long-Term Consequences of Chronic Pain,” at the American Pain Society's(link is external) annual May 2015 meeting in Palm Springs, M. Catherine Bushnell, presented findings from cutting edge research on the ability of yoga to counteract chronic pain that she's spearheading at NIH/NCCIH.

Catherine Bushnell(link is external), PhD, is scientific director of the National Center for Complementary and Integrative Health (NCCIH) at the U.S. National Institutes of Health (NIH) where she oversees a program on the brain’s role in perceiving, modifying, and managing pain. In a press release, Bushnell summed up the findings of her research by saying, "Practicing yoga has the opposite effect on the brain as does chronic pain." 

Bushnell and her colleagues are conducting research aimed at discovering non-pharmacological treatments for pain. They've found that chronic pain can be prevented or reversed through mind-body practices. Lifestyle choices—such as practicing yoga or meditation—have been shown to reduce pain perception and offset the effects of age-related decreases in gray matter volume while helping to maintain white matter integrity. 

Reduced gray matter volume can lead to memory impairment, emotional problems, and decreased cognitive functioning. Hyper-connectivity of white matter tracts between brain areas associated with negative emotions and pain perception can hardwire these corresponding states of mind.

The researchers used diffusion tensor brain imaging to analyze gray matter volume and the integrity of white matter tracts. Bushnell hypothesizes that increased size and connectivity of the insular cortex is probably the most important brain factor regarding changes in an individual's pain tolerance and thresholds.

Yoga appears to bulk up gray matter through neurogenesis and strengthen white matter connectivity through neuroplasticity. After assessing the impact of brain anatomy on pain reduction, Bushnell believes that gray matter changes in the insula or internal structures of the cerebral cortex are the most significant players involved in chronic pain.

"Insula gray matter size correlates with pain tolerance, and increases in insula gray matter can result from ongoing yoga practice," said Bushnell. Yoga practitioners have more gray matter than controls in multiple brain regions, including those involved in pain modulation. Bushnell stated, 

Brain anatomy changes may contribute to mood disorders and other affective and cognitive comorbidities of chronic pain. The encouraging news for people with chronic pain is mind-body practices seem to exert a protective effect on brain gray matter that counteracts the neuroanatomical effects of chronic pain. Some gray matter increases in yogis correspond to duration of yoga practice, which suggests there is a causative link between yoga and gray matter increases.

Rodent studies have shown that increased levels of stress alters pain behaviors, whereas socially and physically enriched environments reduce reduce pain-related brain changes. These findings in both humans and animals indicate that the adverse effects of chronic pain can be reduced, or prevented, by altering environmental factors and making lifestyle choices that improve the pain modulatory systems in the brain.

Yoga Increases Gray Matter Brain Volume and White Matter Connectivity

Bushnell has been working with Chantal Villemure to study the benefits of yoga on chronic pain. In their recent study, they focused on people who had been practicing yoga regularly for at least six years and compared the "yogis(link is external)" to healthy people who didn't practice yoga but were matched for age, sex, education, and other exercise.

Bushnell and Villemure found dramatic differences in gray and white matter between the general population and the yoga practitioners. As Bushnell explains,

We found from brain anatomy studies that the people practicing yoga had more gray matter in a number of regions; as we get older, we lose gray matter, but we didn’t see that decrease in the yoga practitioners, which suggests that yoga may have a neuroprotective effect. When we looked at pain perception, there was a significant increase in pain tolerance in the yoga practitioners, and there was a change in pain thresholds, too.

Villemure has a theory that many of the benefits of yoga might be related to autonomic nervous system and stress reduction as it relates to chronic pain. The autonomic nervous system has two branches: the sympathetic nervous system(link is external) and the parasympathetic nervous system(link is external). Villemure is also examining how yoga practitioners might have a different method of coping with the anticipation of pain.

When most people are expecting pain, it triggers the “fight-or-flight" response of the sympathetic nervous system which causes cortisol levels to skyrocket. On the flip side, Villemure observed that when yogis anticipate pain, their parasympathetic nervous system activates. This creates a "tend-and-befriend" or "rest-and-digest" response, as opposed to a "fight-or-flight" response.

Conclusion: Yoga Is a Viable Drug-Free Treatment Option for Chronic Pain

Most of the pharmacological treatments for chronic pain are opioid based and are highly addictive. Luckily, the effectiveness of non-pharmacological interventions such as yoga and meditation have been shown to have potent pain-relieving effects on the brain. In the long run, alternative treatments for pain, such as yoga, could be more effective than pharmaceutical treatments for relieving chronic pain. 

This article originally appeared on psychologytoday.com and was written by Christopher Bergland.