Is the Time Right for Alternative Therapies?

“It seems that I am wiser than he is to this small extent, that I do not think I know what I do not know."
—Socrates.

The theory of neural plasticity claims that long after a brain is injured it may still retain the ability to repair itself, to regain lost functions by establishing new neural pathways in response to experiences and functional demands. It is an exciting and potentially disruptive way of understanding the brain. The long-held belief that a brain injury survivors’ progress inevitably plateaus after a year or two is increasingly challenged by thought leaders such as Drs. Norman Doidge, Paul Harch, Xavier Figueroa, Carol Henricks, Michael Lewis, Margaret Naeser, David Perlmutter, among others. These physicians cite dramatic cases from their clinical practices of survivors making late-stage recoveries in response to alternative therapies such as, but not limited to hyperbaric oxygen therapy (HBOT), neurofeedback, photobiomodulation, nutraceutical supplementation and craniosacral therapy. They theorize that brain plasticity is the best way to understand such previously unheard of recoveries.

But if alternatives therapies are so great, if they really hold such promise, why are they not more widely embraced by medical professionals? If it turns out that there are persuasive reasons for doctors to steer clear of alternatives, what does that imply for the rest of us? Are those reasons equally compelling for survivors and caregivers?  Scientific proof and understanding of underlying causes is the gold standard in medicine, but what if it is absent? What are we to do about alternatives with long records of safety and mounting evidence of efficacy?  What should a reasonable and prudent person do? The answers to these questions are complex. If we untangle the threads, we may find a perspective from which to view safe alternatives in ways that help everyone involved in the circle of care – patients, caregivers, therapists, allied health professionals, and yes, even doctors and hospitals.

Physicians avoid alternatives for several reasons: They receive little if any exposure to them during their extensive education, no encouragement from their conservative professional culture, and no business incentive in their practices. If these influences weren’t enough, there may be serious hazards facing doctors who try alternatives. It exposes them to malpractice lawsuits when, inevitably, a patient is unsatisfied with an outcome.  Worse, they risk being disciplined by local medical societies and boards for using unconventional treatments, and in extreme cases, may even be censored, lose their license or face criminal charges, lodged by the FDA or others. Practitioners of safe alternatives have sometimes suffered these dire consequences. So for physicians there may be a high practical price to be paid for trying alternative therapies which, if they simply avoid, they cannot be faulted. We have met doctors who acknowledge being intrigued by the prospect of trying alternatives, but deterred by possible practical consequences.  It’s hard to fault them. It seems a truism, but even the best-trained, most skilled, and well-intentioned professionals in the world often suffer a kind of tunnel vision, sticking to familiar, well-trod paths that pioneers once blazed.

In his groundbreaking book When Brains Collide, Dr. Michael Lewis, Col. US Army (Ret.), rejoices that soldiers wounded in combat can be kept alive even after suffering devastating TBIs, thanks to dramatic improvements in emergency medicine and surgery. But since treatments for chronic brain injuries have not kept pace, he laments that afterwards often one can do little more than warehouse them in nursing homes. That is our starting place. Conventional medicine only takes survivors of severe brain injury so far, often ending at the nursing home door, or heavily medicated at home, facing long empty hours, and overwhelming family resources.

It may, after all, turn out that nothing more can be done. If there is any hope of improving these grim outcomes, it falls to those of us living with the consequences of inaction to keep an open mind, think outside the box and cautiously explore alternatives.  This seems to be the nub of the matter: Faced with a condition for which mainstream medicine has no satisfactory treatment, what should a reasonable and prudent person do? Accept the dismal verdict or cautiously explore alternatives? What harm is there in considering alternatives with long records of proven safety? For physicians, the obvious bar is the risks associated with running afoul of FDA approval. Costing tens of millions of dollars, the FDA process often effectively precludes alternative therapies from gaining traction– regardless of efficacy. But a therapy may have a good deal of supporting evidence, yet fail to meet the standards of FDA approval. And if safety can be reasonably assured, why not explore further? Our family felt compelled to do so after our teenage son suffered a severe brain injury in a car crash.

Nearly a year after Bart’s catastrophic injury he continued to suffer from crippling cognitive, emotive and physical deficits.  The school district and rehab hospital both agreed - he was not ready to return to class, and would be better served by placement in an institution. My wife, Dayle, and I balked at warehousing our 17 year old in a nursing home. We felt that he needed to be home, around familiar faces, among people who loved him, to have even a fighting chance at recovery. Over officials’ objections, we managed to bring him back home and into school, albeit in a highly modified and adaptive special ed. program. It was soon apparent that he was failing to meet even modest educational and therapeutic goals. 

Desperate, Dayle and I turned to alternatives in a last-ditch effort to keep him home and in school.  As we were arranging for him to receive HBOT, a neurologist warned that it was a waste of time and money, even scolding the director of the HBOT clinic for holding out false hope to a family frantically clutching at straws. In his clinical experience, he had never seen patients improve through recourse to HBOT or any other alternatives. Survivors’ recoveries routinely plateaued after a year or so, and there was nothing more for it. His blanket rejection of alternatives was not bad faith or ill will, but authentically reflected years of clinical experience. (Contrary anecdotes were dismissed as spontaneous improvement, placebo, wishful thinking, and old wives tales…certainly not considered evidence). Nonetheless, we persisted with HBOT and Bart began to make dramatic, cumulative, lasting strides. We dedicated the book which recounts his recovery, No Stone Unturned, to the clinic’s director, Dr. Guisippina Feingold. That was 2002. Not much has changed – I recently heard a neurologist on NPR, and several at BIA conferences confidently declare that HBOT as treatment for ABI is not evidence-based. What they probably meant was that HBOT is not FDA approved as treatment for ABI. Pressed further, they may have referred to an absence of double-blind placebo trials – the gold standard in medicine. Since HBOT is the alternative therapy with the strongest supporting evidence, and which more than any other drove Bart’s recovery, let us take a deeper look at what seems to be the consensus opinion among physicians - that there is little or no hard evidence supporting HBOT.

What exactly is involved in HBOT? The patient is placed in a diving bell which is gradually pressurized to approximately 1.5 atmospheric pressures, the equivalent of being underneath 16 feet of water. The cabin is then flooded with pure oxygen, which the patient breathes for an hour or more. Normally oxygen, which constitutes 21% of the air we breathe, only enters the bloodstream one way — picked up in the lungs and carried via red blood cells to the body’s tissues. But breathing pure oxygen under pressure overwhelms the capacity of red blood cells, so blood plasma and other bodily fluids become saturated with oxygen — up to fifteen times the amount normally available.  Excess oxygen helps injured sites heal, by allowing them to revascularize – to re-grow the network of tiny arterioles and capillaries supplying blood to the injured tissue, a process known as angiogenesis. The new blood supply does the serious work of healing – removing toxins and bringing in needed oxygen, energy and other healing building blocks. That HBOT promotes healing is well established. Burn centers use it to speed recovery and reduce scarring. There are 14 conditions approved by the FDA for treatment with HBOT; acquired brain injury (ABI) is not among them.¹

What about the claim that there are no double-blind placebo studies? It’s true. There are serious practical, logistical and even ethical obstacles to creating a true placebo when studying HBOT. It is not as simple as using a sugar tablet or gelatin capsule, as is often done in experimental trials of new drugs. In order to design a placebo control group for HBOT, one must create experimental conditions which, while simulating HBOT, have no therapeutic effect.  Why should that be a problem? Because “placebo” HBOT needs to have increased pressure in the chamber so that the subjective experience for the patient is indistinguishable from the therapeutic dose. But using ordinary air under pressure of 1.3 ATAs (the level at which a person can detect pressurization) increases oxygen saturation of blood by 50% - an increase which has been shown to yield therapeutic improvements. So if one were to set up a control or sham with room air at 1.3 ATA, the pressure itself may be responsible for a therapeutic increase of blood oxygen. Under such a protocol both trial and control groups are delivered increased doses of oxygen. Imagine testing whether aspirin reduces headaches by giving the trial group an aspirin, and the control group half an aspirin, rather than a sugar tablet. The only way to guarantee no increase of blood oxygen in the control group (and thus no therapeutic effect), would be to reduce the amount of O2 in air from roughly 20% to around 10% and then pressurize it back to 20%. But doing so is unethical, as it may cause harm.

So Israeli scientists did the next best thing - cross-over studies. Patients were divided into two groups: a trial group received HBOT; a control group received no treatment. After being closely monitored for 8 weeks, the trial group receiving HBOT was seen to make significant improvements, whereas the control group did not. Then the control group was also treated with HBOT and seen to make the same improvements as had the trial group, including functional gains measured by standardized tests of cognition and quality of life. SPECT scans showed greatly increased blood profusion in injured regions of the brain, averaging 40%. Analyses of scans were done blind to enhance reliability. Further laboratory studies also gave evidence of elevated brain activity, reduced inflammation, release of genes involved in healing, and increased production of neural stem cells. The Israeli investigators concluded: “HBOT can induce neuroplasticity leading to repair of chronically impaired brain functions and improved quality of life in mTBI (mild TBI) patients with prolonged PCS (post-concussion syndrome) at late chronic stage.” (Notably, participants were 1 to 5 years post-injury, to rule out spontaneous improvements which may occur in the first year after injury).²

Subsequent cross-over studies of stroke and other anoxic brain injuries all showed similar results – dramatically increased blood flow and brain activity accompanied by improved cognitive function and quality of life. HBOT seems to have neuroprotective effects, promoting vital healing processes in the brain, even in the chronic stage.

As a result of these studies, in 2015 Israel made HBOT part of the standard treatment for most brain injuries. Can it be that HBOT is evidence-based in Israel but not here in the States? Suppose one resides in a third country, say Spain. Should one travel to the US for best-in-class treatment absent HBOT, or fly to Israel and receive HBOT as a matter of course? What would a reasonable and prudent person do?  Perhaps wait and see. Clinical trials currently underway in the US - New Orleans under Dr. Paul Harch, and Florida under Dr. Barry Miskin, - both use similar top-tier designs and are beginning to replicate the Israeli results.³

That is not the end of the story – it seems there is more drama underlying the controversy surrounding HBOT. A couple of well-publicized studies by the Veterans Administration (VA) concluded that HBOT’s effects are mere placebo. Their designs were flawed. Control groups were given ordinary air at 1.3 ATA. As we have noted, that may be a low therapeutic dose of O2, so the investigators never created a genuine control group. They did not bother checking with experts in hyperbaric medicine about best practices – even their trial group was given non-optimal air pressure. It would be fair to say that that the VA botched both trial and control groups.  When it turned out that both groups showed improvements, (presumably due to increased oxygen availability) the investigators erroneously concluded that HBOT is mere placebo, instead of realizing they had demonstrated that increased blood oxygen, even by varying amounts, led to improved outcomes. The prominence of the VA studies has set-back hyperbaric medicine here in the States. Taking the VA results at face value, the FDA subsequently issued a warning to physicians and the public against using HBOT for neurological conditions. Small wonder neurologists continue to believe that HBOT is not supported by evidence.

Recently an author of the original VA study, Dr. George Wolf, published a new analysis of his original data, and revised his conclusions: “There is a potential gain and no potential loss. The VA/Clinical Practice Guidelines define a “B evidence rating” as “a recommendation that clinicians provide (the service) to eligible patients. At least fair evidence was found that the intervention improves health outcomes and concludes that benefits outweigh harm.”⁴

HBOT currently has 14 FDA approved uses. It is relatively safe. Compared to side effects of commonly prescribed medications for seizures, anxiety, and other brain issues – it is extremely safe. The mechanisms of healing are fairly well understood, and seem to be the same regardless of the injury, so why not allow off-label use to treat brain injuries?  In fact nearly all medications prescribed by neurologists to manage ABI are done so off-label. For those of us in the trenches, with the most skin in the game, what is the reasonable and prudent course of action?

There are several other safe alternative therapies worth mentioning: Neurofeedback, craniosacral, photobiomodulation (not a pretty word, meaning low level light devices), transcranial magnetic stimulation, the PoNS devise, neutraceutical supplementation especially omega-3 fish oils, among others.

Let’s take a closer look at what has been called “the poor man’s HBOT:” Omega-3 supplementation. Here we move from the most expensive alternative to the least. (The average cost for an optimal course of HBOT at an independent clinic is $12K-$20K, compared to several hundred dollars for a year’s dose of fish oils). Twelve years after Bart’s injury, we were lucky enough to hear from Dr. Michael Lewis. An army physician in Iraq, he had extensive experience treating soldiers with severe blast-induced TBI’s. Delivering massive doses of Omega-3s through feeding tubes, he found that the soldiers often rapidly improved, some even emerging from vegetative states. Since retiring from the army, Lewis has modified that protocol so that patients can take the oils orally.

After we were satisfied that mega doses of Omega-3’s would do no harm, we decided to give them a try. Twelve years post-injury, Bart had learned to cope with the loss of fine motor control on his right side by using his left hand for everyday tasks like eating, though rather clumsily. When occupational therapy had been discontinued 10 years earlier, his right hand use had been rated at 15-18%. After 3 months on Lewis’ protocol, we went out for Mother’s Day dinner to a Chinese restaurant. With a dramatic flourish, Bart picked up chopsticks with his right hand and, smiling sheepishly, ate his meal flawlessly. He’s now writing, eating, even playing guitar - right side dominant again after a 12 year hiatus. He probably has 60-65% fine motor control - a 200% improvement! There is hardly any precedent for this sort of late-stage recovery.

How was that possible? Some remarkable facts about Omega-3 fatty acids may help: The brain is constituted roughly one-third by omega-3 fatty acids (EPA and DHA).  They equal the dry weight of the brain! Omega-3s are the foundation of the neuron’s cell membrane – the bricks of the brain. Dr. Lewis’ metaphor is of a brick out-house that is blown up in an IED explosion. When we pour in fresh bricks, the brain begins to rebuild itself. Besides being the very stuff of the brain, Omegs-3s provide a “neuropermissive” environment for healing; they douse the harmful inflammation and other destructive biochemical processes cascading through the injured brain. 

Lewis’ protocol for Omega-3 administration – first by feeding tube, then later by oral administration, calls for huge doses. Patients report clearer thinking, improved energy, reduced irritability, fewer headaches, and improved sleep. The FDA has long classified as much as 3000 mg daily Omega-3s GRAS – generally recognized as safe. There are practically no adverse reactions or significant drug interactions. Like all alternatives, it is safest to employ them under the oversight or guidance of a health professional.

There is mounting preclinical and clinical evidence of Omega-3’s effectiveness in helping heal brain injuries.  Independent studies show that it may lower blood pressure and triglyceride levels, help prevent and manage heart disease, fend off Alzheimer’s, control ADHD, and reduce depression. A recent long term study showed older women with high levels of DHA and EPA in their blood were 20% less likely to die from any cause. That’s 20% reduction in overall mortality! What other supplements can make a similar claim?⁵

Two respected peer groups of scientists endorse the use of Omega-3s for nutritional support therapy during the acute stage of brain injuries: American Society for Parenteral and Enteral Nutrition (ASPEN) (i.e. intravenous and feeding tube nutrition), and the Society for Critical Care Medicine (SCCM). In 2016 both organizations recommended Omega-3 supplementation through feeding tube for patients with ABI. Unfortunately most doctors do not find time to read or follow these guidelines. But as caregivers we can hope to educate them. Such recommendations may carry considerable weight with physicians, since these organizations maintain strict scientific standards and are not generally known to advocate alternatives.

Here is the crux of the matter: While Omega-3s are not yet scientifically proven to resolve brain injury issues, they are an essential nutrient, generally regarded as safe, with growing evidence of effectiveness across a range of ailments, and endorsed by relevant organizations of experts. What should a reasonable and prudent person do? What is the downside? What is the risk? Why not try them? Other therapies mentioned also have some scientific evidence supporting their effectiveness, but are far more expensive and logistically difficult to obtain than fish oils.

Faced with the sprawling chaos of ‘alternative therapies,’ and painfully aware that a false step might risk further injury to a loved one, one might well be staggered. How can one determine which approaches are safe and hold real promise?  

In a spirit of cautious hope, fifteen years ago Dayle and I set out to cobble together an unofficial “medical board” of trusted physicians. “Members” didn’t know each other or that they served on a “board.” When we found a promising alternative therapy, we’d ask each whether she thought it might do any harm. Those that got a clean bill of health, moved to the next stage for further investigation.  Some of the most promising and exciting approaches failed this simple Hippocratic test. Our bags were packed a couple of times, only to be shot down by a “board” member seeing potential harm in an emerging therapy. TBI is a life-long condition, and we rely on this basic method to this day. 

Building on those early efforts, the BART Foundation advocates a pragmatic approach to dealing with intractable brain conditions. Its First Principle is the Hippocratic one - do no harm. The safety of a potential therapy must be vetted by experts. Relying on intuition or common sense will not suffice. Our panel of medical experts assesses the relative safety of alternatives, and advocates for ones with a high degree of safety. Seems nothing is 100% safe and effective - not even aspirin or acetaminophen. HBOT, used safely for over 100 years by deep sea divers, and FDA approved for 14 conditions including life-threatening ones such as gangrene and radiation burns, clears the safety hurdle with flying colors. So does Omega-3 supplementation and several other alternatives. Not everyone has access to such a team of experts, but your family physician, PA, nurse practitioner, public health officer, neurologist or neurosurgeon are good places to start. Remember – you’re not inquiring whether a therapy is likely to help – only if it is safe.

Once safety is assured, you may wish to go on to explore how strong is the evidence. What additional vetting can be done?  The background process involves searching the scientific literature, speaking with caregivers, practitioners, and other responsible parties including manufacturers.  There are no money-back guarantees, no credible assurance of success. After safety and effectiveness are relatively well established - it may be time to take the leap. It is, after all, a leap of faith. Best in class treatments, mainstream as well as alternative, do not work for every patient. 

When a loved one suffers a brain injury we suddenly find ourselves thrust into a harsh alien landscape, trying to navigate with no clear roadmap or sure-fire formula for success. We may explore alternatives paths, yet still fail to come up with an approach that produces a better outcome. On the other hand, to ignore safe alternative therapies is to make a decision fraught with other risks, since survivors are already more vulnerable to a number of conditions including Alzheimer’s, Parkinson’s, and subsequent TBIs.   Faced with this existential dilemma, our family chose to try for a better outcome. We were lucky that several alternatives drove Bart’s recovery far beyond expectations. Today he is a lively charming young man living semi-independently in his own apartment, with a part-time job, new friends, uses a computer and Smartphone for communicating via a variety of social media and joins me in presentations to brain injury groups as a survivor-advocate.  How different his life would be had we followed the advice of well-meaning busy officials. The BART Foundation hopes to spread awareness of safe alternatives so that families on similar journeys have a better chance at sharing that kind of luck. We hope you consider alternatives when you come to that fork in the road. Those depending on you, in your care, might leave nursing homes, or if already in the community, cut back on their meds and live more fulfilling and productive lives.⁶

Footnotes:

1. HBOT is FDA approved for the following 14 conditions: air or gas embolism; carbon monoxide poisoning and smoke inhalation; clostridial myonecrosis (gas gangrene); crush injury, compartment  syndrome and other acute traumatic ischemias; decompression sickness; enhanced healing  of selected problem wounds; exceptional blood loss anemia; necrotizing soft tissue infections;  osteomyelitis (refractory); radiation tissue damage (osteoradionecrosis); compromised skin  flaps and grafts; thermal burns; and, intracranial abscess.
   
   Dr. Carol Henricks summarizes the healing mechanisms involved in HBOT: HBOT creates oxygen radicals, which stimulate healing mechanisms including production of neurotrophic growth factors and vascular endothelial growth factor, neural stem cell proliferation and mobilization, and modification of gene expression. Journal of American Physicians and Surgeons Volume 22 Number 2 Summer 2017 Traumatic Brain Injury Can Be Healed, Timothy Marshall, Ph.D., and Carol Henricks, M.D.
2. Hyperbaric Oxygen Therapy Can Improve Post Concussion Syndrome Years after Mild Traumatic Brain Injury - Randomized Prospective Trial; Rahav Boussi-Gross , Haim Golan , Gregori Fishlev, Yair Bechor, Olga Volkov, Jacob Bergan, Mony Friedman, Dan Hoofien, Nathan Shlamkovitch, Eshel Ben-Jacob , Shai Efrati .Published: November 15, 2013 https://doi.org/10.1371/journal.pone.0079995
3. Dr. Paul Harch, dean of hyperbaric medicine in the States, recently published his results in Medical Gas Research, Volume 7, Issue 3, September 2017.  HBOT was found to be safe and significantly effective for veterans with mild to moderate TBI with persistent postconcussive symptoms (PPCS) and PTSD. The full study can be downloaded at Treatnow.org’s website: http://treatnow.org/harch-medgasres-hbot-tbi-ppcs-ptsd/
4. Wolf remarks: Undersea Hyperb Med. 2015 Jul-Aug;42(4):313-32. Cognitive function in a traumatic brain injury hyperbaric oxygen randomized trial. Wolf EG, Baugh LM, Kabban CM, Richards MF, Prye J.
5. Longitudinal study of women and Omega-3s. Harris, W.S., Luo, J., Pottala, J.V., et al. J Clin Lipidology (2017). doi: 10.1016/j.jacl.2016.12.013
6. Even absent FDA approval, there is an emerging acceptance of HBOT and other safe alternatives. A movement is underway to make HBOT available free of charge to wounded veterans -Treatnow.org and Patriot Clinics are leaders in that field. The states of Oklahoma and more recently Texas have passed bills funding such treatment.  The VA and DOD are selectively using HBOT, neurofeedback, acupuncture, craniosacral, meditation and other alternatives. And so it goes, brick by brick.

Joel Goldstein is father of a TBI survivor, writer and advocate. Author of No Stone Unturned: A Father’s Memoir of his Son’s Encounter with Traumatic Brain Injury (University of Nebraska Press, 2012), he has written for Brainline.org, Exceptional Parent, Caregiver Space, and Adoption Today. In 2016, along with several distinguished physicians, Goldstein formed the Brain Alternative Rehabilitation Therapies Foundation (BART Foundation), a 501(c)(3) public charity, to explore and promote use of safe alternative therapies for brain injuries. To learn more about the foundation visit: www.thebartfoundation.org. To learn more about the Goldstein family’s journey: www.tbibook.com. He can be reached at jgoldstein@thebartfoundation.org