>> July 1998

Abstract

Fifty stable, chronic stroke and traumatic brain injury (TBI) patients (mean age 62, mean duration post stroke 29 months) were treated with a combination of hyperbaric oxygen, physical therapy and EEG biofeedback for two months. Surveys given to patients or their family members showed that 96.7% of the patients improved one or more of their lost or diminished functions. Pre- and post-treatment, physical therapy evaluations indicated that 100% of the patients experienced improvements in one or more functions. These results suggest hyperbaric oxygen therapy along with other modalities provide safe and efficient treatment of stroke or TBI related disabilities.

Introduction

Health institutes have shown different efforts to improve the quality of daily life for stroke patients. However, the general outcome is not a encouragement, especially for those of long term stroke or brain injury related disorders (TBI) patients. Although stroke is a leading cause of death and disability, its post management was often marked by feelings of hopelessness.

Hyperbaric oxygen therapy (HBO) uses oxygen under pressure and first clinical use of hyperbaric oxygen for treatment of stroke and TBI patients was reported in 1965. Since then many studies have demonstrated its safety and efficacy (1,2,16-20). It is expected that HBO will be a competitive therapy for this devastating neurological disorder.

The dominant theory of stroke and TBI for more than 100 years has been that the loss of function is largely related to the death of brain cells due to the interruption of blood flow and the resulting lack of oxygen to a part of the brain. This traditional concept of infarction is being challenged by a theory which has been slowly evolving over the past 25 years. This theory states that the death of brain cells occurs only when the flow of blood falls below a certain level (approximately 8-10 ml/100 gr./min., while at slightly higher levels of blood flow the tissue remains alive but not able to function. Thus in the acute stroke the affected central core of brain tissue dies while the more peripheral tissues may remain alive for many years after the initial insult, depending on the amount of blood the brain tissue receives (3,7).

Brain areas that are injured and are not receiving enough blood flow as a result of the stroke or trauma are now referred to as the "ischemic penumbra". This is the area that surrounds the central core of infracted (dead) tissue. These "rim" tissues do not receive enough oxygen to function but do receive enough to stay alive. These brain cells have been described as "sleeping beauties", "sleeping neurons" or "dormant" or "idling neurons". These neurons are nonfunctional but anatomically intact and can be revived. ( 3), (8-10).

It is widely recognized that damaged blood vessels are thought to produce the ischemic penumbra in stroke or TBI. In the acute phase of stroke or TBI, those damaged blood vessels lead to significant edema (swelling of the tissues as a result of the damage). This swelling may take up to 9 to 12 months to resolve, and the swelling compresses brain blood vessels, limits the flow of blood to the damaged tissues. As the swelling goes away, some of the blood vessels will regain their original diameters and normal blood flow will resume (9). It was widely documented that the water content of edematous tissue of the brain was decreased significantly by HBO. (12­14).

Another process is "neovascularization", also known as "angiogenesis". This is the process of forming new capillaries that extend from the surrounding healthy brain tissue into the areas of the ischemic penumbra. The outermost portions of the ischemic penumbra (those portions closest to normal brain tissue) are able to metabolize but at a reduced rate than normal tissues, however, they are receiving more blood and oxygen than the centrally located ischemic tissues. Adenosine, a metabolite of ATP, is released from ischemic "rim" tissues when cells metabolism and repair. Adenosine is a vasodilator that stimulates new capillaries to grow into the ischemic penumbra (neovascularization). Thus during the first year after a stroke or TBI, new blood vessels are stimulated to move into the ischemic penumbra to re-supply it with a new blood supply. (9) Unfortunately, the ischemic penumbral tissues closer to the infarct area usually are not receiving enough oxygen or nutrients to generate adequate amounts of ATP - either from aerobic or anaerobic metabolism for neovascularization to occur. Due to the lack of ATP formation, adenosine is not produced and the formation of new capillaries does not occur. Thus the ischemic penumbra remains ischemic and static since the process of neovascularization is not able to be completed. This often results in a substantial amount of brain tissue that remains ischemic and non-functioning in the chronic stroke and TBI patients. This failure of natural healing processes is due ultimately to damaged blood vessels and their inability to provide oxygen and nutrients to those portions of the brain that are damaged.(11)

Hyperbaric oxygen works to improve chronic stroke and TBI patients by regenerating, repairing and generating new blood vessels to the injured parts of the brain. In the ischemic penumbra, the blood vessels are often constricted to the point that red blood cells cannot pass through them. This creates the situation where only plasma is able to pass slowly to part or most of the ischemic area. Since plasma has nutrients, the tissues of the ischemic penumbra are able to remain alive by using anaerobic glycolysis (metabolism without oxygen) also known as fermentation.. Anaerobic glycolysis only produces 2 moles of ATP per mole of glucose metabolized instead of the 36 moles of ATP formed when oxygen is present. Thus the tissues suffer from a chronic shortage of ATP and its subsequent metabolite- adenosine. Hyperbaric oxygen forces oxygen into the plasma to such a degree that as the plasma passes into the ischemic penumbra, the ischemic tissue begins to receive enough oxygen for aerobic glycolysis (metabolism that uses oxygen) to occur once more. This creates a surge of ATP production in the ischemic tissue which continues to be produced as long as the patient is within the hyperbaric oxygen chamber. When the patient is taken out of the chamber, blood and tissue levels of oxygen fall back to pre­treatment levels within 4 hours. As the tissue oxygen level falls, the newly generated ATP is used by the ischemic tissues and adenosine is released into the surrounding tissues in an effort by the tissues to continue to receive the oxygen that it just had been receiving. As a part of this survival mechanism, adenosine and other chemical mediators are released into the surrounding tissues stimulating angiogenesis. Done daily over time, the HBO stimulates new blood vessels to grow into the ischemic tissues returning them back to normal in terms of their oxygen supply. Recovery of function is associated with recovery of local perfusion and metabolism. (11)

Once the ischemic penumbral tissues are no longer suffering from a lack of oxygen, they are able to begin to repair their injured neurons, glial cells and extracellular matrix. These tissues now have to try to repair their own cell bodies, dendrites, axons and synapses but also have to grow out and extend to the many lost connections that occurred with the stroke.

Treatment of acute and chronic focal cerebral ischemia with hyperbaric oxygen has been reported both in animal and in humans. The results of the clinical research have suggested a promising role for the use of HBO. (2, 16-20). In this study, we showed that HBO is quite effucient when used as a part of combined therapy and patients did benefit from this therapy.