Dr Shai EfratiShai Efrati, MD
Hyperbaric oxygen therapy, which has been approved by the FDA for 13 different indications, had yet to be studied for cognitive challenges until recently, in which data suggests that it may offer new hope for stroke patients.

Led by Shai Efrati, MD, director, Sagol Center for Hyperbaric Medicine and Research, a group of researchers have been assessing the effects of hyperbaric oxygen therapy in improving memory impairments in patients with stroke, as well as inducing late neuroplasticity in these patients. Findings suggest that hyperbaric treatments offer statistically significant improvements in all memory measures and indicate that it can lead to significant neurological improvements in post-stroke patients even at chronic late stages.1,2

To learn more about this potential post-stroke intervention, NeurologyLive spoke with Efrati in an interview.

NeurologyLive: How long have you been exploring hyperbaric oxygen therapy, in cognitive conditions or otherwise?

Shai Efrati, MD: Generally speaking, the indication for hyperbaric oxygen is for ischemic non-healing wounds. Non-healing wounds normally in the periphery of the leg, and for some conditions due to diabetes. This is where the approved indication is today. Our perspective is we are looking at the brain as a tissue. A tissue where the basic justification of the need in order to heal the tissue generally more or less the same, like the wounds that we have in their legs, meaning, if the great limiting factor for the wound repair is lack of oxygen supply or insufficient oxygen supply, then this wound will not heal. And the main goal is to look at the brain in the same manner that we are looking at ulcer in the leg, and not differently. Even though we're looking at the brain in a contralateral parenchymal enhancement MRI, which is high tech—and speaking about the brain in a mystic fashion cognition, personality, and emotion—at the end, it is a tissue.

Something like 10 years ago, we triggered an ongoing research program that is aiming to treat the non-healing wounds that we see in the brain. Part of this research program is a stroke. And what usually happens in stroke is that we have an area that doesn't get sufficient oxygen supply, due to occlusion or due to hemorrhage, and because of that there is damage to the brain tissue. There are several degrees of damage to the brain tissue, and the most severe one is necrosis because the tissue is fully dead, there's nothing there. In the instance where we have necrotic tissue, there is nothing we can do. But in the surrounding tissue, there might be tissue that is not fully dead, that is damaged. In this tissue, we have metabolic dysfunction. The cells in this area have sufficient oxygen supply to stay alive, but they don't have the full energy needed for the full activation. This is where hyperbaric oxygen can help. The challenge is to be able to demonstrate this. In order to do so, we are using a combination of brain imaging, a combination of anatomical imaging of the brain that is mixed up together, combined with metabolic imaging of the brain. The anatomical imaging of the brain can be either CT or high-resolution MRI, and the metabolic imaging of the brain can be either SPECT/CT or different protocol of functional MRI.

The areas that we see in the brain that is not fully dead, that is not fully necrotic, and still do not have full metabolic activity, this is the area that can be rejuvenated with the hyperbaric oxygen treatment. This is where we can help. The clinical improvement would depend on this area. For example, if this area is responsible for the hand movements, then the hand will move, and if the leg, then the leg. By doing so we can set the expectation with the patient. If it's the Broca's area, then the speaking capability will improve. If we don't see that area, then the patient is not suitable for the treatment.

What current research is being undertaken in this field?

In the first study, our focus was on poststroke patients, was on the muscle function. We took a patient that has a clear motor function, meaning they could not move the hand, the legs, things like that. We took 74 patients, more than 6 months after their event, not because this is the classical time for the treatment, but because we didn't want the control group to improve. They were randomized either to the treatment group or this control group. And in this study, we can clearly demonstrate clinical improvement. But more importantly, we can see the correlation between the clinical improvement with the rejuvenated brain tissue to the metabolic brain tissue that is reactivated. This was the first study that was focused on motor function.

In continuation of that, the next study was focused on the cognitive, especially on the memory. When we are speaking about stroke patients, we are usually focused on their motor disabilities. Can they walk and use their hands? Can they speak? And we are quite neglecting the cognitive disturbance that's happened after the stroke. In the next study, we were focusing on cognitive improvement, and to be more specific, on the memory. Again, we were able to demonstrate the improvement in the memory function. But more importantly, it could be correlated to the reactivation or rejuvenation, of the specific area in the brain that is related to that.

Are physicians utilizing this as much as they could be?

It's not widely used yet because as you know, it takes time. These are the first studies. In addition to our study, there are other centers now that are doing research, understanding better where it can help and who are the cohorts that can benefit the most. It will take time, but this is a huge advancement. And it's more than that, it's changed the paradigm of how we look at the brain and what is needed for the brain. This is very important.

Unfortunately, not every location will have the capabilities to do both the brain imaging—the metabolic anatomical—together with the hyperbaric oxygen therapy, but it will come. This is a start and more studies are on the way, and we will accumulate more and more data.  But this is very promising and very exciting, especially the correlation with what we see in the brain, the changes—our ability to see the changes in the brain in addition to the clinical improvement.

Are there subgroups that have shown particular benefit at this point?

We are not too early, there is an ongoing research program, we'd really like to do that. Because once you understand that you need to specify a wound. So this wound can be either due to stroke or due to a traumatic brain injury. As long as you see the brain and see the specific wound that is suitable for the hyperbaric treatment, as long as you evaluate the wound and not the clinical presentation, that's opened a whole new area—stroke, TBI, anoxic brain damage. In addition to the stroke study, we have also an ongoing research program related to TBI to traumatic brain injury, seeking the same perspective and the same understanding of where hyperbaric can help, and how to select the patients.

What should clinicians know about the use of these methods?

What we learned thus far is that we can characterize the wound in the brain, and if we see an area that is not fully dead, that has metabolic dysfunction—still there, but not fully active—there is a chance for recovery of this area, even years after the acute instance, we are taking patients years after that instance—as long as we see this area. That's a new hope, and that brings a new approach, a new treatment approach to these patients, who unfortunately up to now didn't have any good intervention that can rejuvenate the damaged brain tissue.

Transcript edited for clarity.
REFERENCES
1. Efrati S, Fishlev G, Bechor Y, et al. Hyperbaric oxygen induces late neuroplasticity in post stroke patients--randomized, prospective trial. PLoS One. 2013;8(1):e53716. doi: 10.1371/journal.pone.0053716.
2. Boussi-Gross R, Golan H, Volkov O, et al. Improvement of memory impairments in poststroke patients by hyperbaric oxygen therapy. Neuropsychology. 2015;29(4):610-21. doi: 10.1037/neu0000149.