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A BRIEF REVIEW OF HYPERBARIC OXYGEN
FOR STROKE REHABILITATION
David A. Steenblock, M.S., D.O.
Oxygen is a natural gas that is absolutely necessary for life and healing. Purified oxygen is defined as a drug but is the most natural of all drugs. Oxygen under pressure is still the same gas but is more able to penetrate into parts of the body where the arterial flow is hindered - producing ischemia (loss of blood flow) and hypoxia ( lack of oxygen). When oxygen under pressure is breathed by a patient in a sealed chamber it is termed a hyperbaric oxygen treatment (HBOT). The treatment lasts from 45 to 120 minutes during which time the person’s body is surrounded by air pressure equivalent to the pressure produced by diving 16 to 33 feet underwater (7.35 to 14.7 pounds per square inch = 1.5 to 2 ATA).
In addition to raising the arterial levels of oxygen 10 to 15 times higher than that produced by normal atmospheric pressure, the pressure exerted within the body can and does exert therapeutic benefits on acute and chronically traumatized and swollen tissues.
The first suggestion that raised air pressures might be used in the treatment of human illness was made in 1664 by Henshaw in England. The first hyperbaric chamber to investigate the therapeutic action of compression of the air on the human body was described and built by Junod in 1834. Using 1 1/2 atmospheres of pressure, Junod was reported to have treated patients with paralysis with beneficial results. This pioneering work was not continued until 1965 when Ingevar and Lassen demonstrated positive results in 4 patients suffering from focal cerebral ischemia. Since then, numerous articles have been published demonstrating that hyperbaric oxygen is useful for the treatment of both acute and chronic stroke.
A sound physiological and anatomical basis for why hyperbaric oxygen improves acute and chronic stroke and brain damaged individuals has been developed over the past 100 years.
NEUROPATHOLOGY
In 1908, R. Pfeifer reported autopsy studies of human brains that had undergone exploratory punctures, months before their deaths. He recognized on the margins of the resulting brain injuries that the scars had numerous nerves and nerve fibres that were regenerating.
That these "marginal" neurons remain intact, alive and in place for more than the few months reported by Pfeifer was reported in 1934. Cyril B. Courville demonstrated the persistence of the processes of disintegration, of phagocytosis and repair in the brain of a 57 year old who had been shot in the head twenty-two years previously. Seriously damaged nerve cells had maintained their morphologic identity throughout this long period. In summarizing this case Courville stated, " Morphologically, crippled nerve cells may persist in the margins of wounds of the brain for many years." "Even after a prolonged interval the larger nerve fibers continue to show regressive change at the margins of wounds of the brain."
The concept of an ischemic marginal zone surrounding a central core of infarcted brain tissue as a component of stroke induced damage was further developed by Astrup, Symon, Branston, and Lassen in 1977. Their baboon studies showed that electrical activity was lost at the periphery of a cerebral infarct when the blood flow fell below 15 ml/100g/min while neuronal death began to occur when blood flow fell to 6-8 ml/100 g/min. These low blood flow values may be used to define an area surrounding an infarct where the tissues remain alive but are not functioning called the "ischemic Penumbra". Dorland’s Illustrated Medical Dictionary (28th ed., 1994) defines the ischemic penumbra as "an area of moderately ischemic brain tissue surrounding an area of more severe ischemia; blood flow to this area may be enhanced in order to prevent the spread of a cerebral infarction." Results have accumulated supporting the concept of the ischemic penumbra as a dynamic process of impaired perfusion and metabolism eventually propagating with time from the center of ischemia to the neighboring tissue. As mediators and modulators of this process, waves of depolarization, extracellular increases in excitatory amino acids, activation of Ca++ channels, intracellular calcium deposition, induction of immediate early genes and expression of heat-shock proteins all play a role.(Heiss, WD, Graf, R 1994)
Spontaneous electrical activity is impaired when cerebral blood flow is reduced to about 60% of control. (Hossmann, KA et al 1980) (Moraweth RB et al 1979) Protein synthesis is suppressed 50% at a cerebral blood flow of 40% even before spontaneous electrical activity is impaired. (Mies, G. et al. 1991).
Branston (et al 1974) demonstrated a deterioration in the amplitude of somatically evoked potentials at approximately 34% of control blood flow which is also the level of blood flow at which glucose begins to be utilized more rapidly due to oxygen-debt inhibition of mitochondrial metabolism and oxidative phosphorylation. Thus glycolysis is stimulated in order to maintain ATP levels. This produces lactic acid which accumulates because flow is reduced. Since ATP production by glycolysis cannot fully compensate for oxidative phosphorylation, AMP and purine levels increase and tissue adenylates are irreversibly lost either enzymatically or through blood clearance. Reduction in cerebral blood flow below 30 ml/100 g/min supresses the adenylate cyclase and protein kinase C system (Tanaka K et al. 1993). The loss of adenylates, accumulation of lactic acid with a lowering of the pH and the formation of free radicals with subsequent oxidation of blood vessels walls, blood components and brain tissues results in induction of early response genes, expression of heat-shock proteins and diminished blood vessel wall and brain tissue protein synthesis and responsiveness (Paschen, W. et al 1992) (Newman, GC NIHR01Ns28429-02) Other studies have implicated a multifactorial interaction at the ischemic blood-endothelial interface of Factor Vlll/von Willebrand factor, prostanoids, leukocytes, platelets, platelet-activating factor, leukotrienes, adhesion receptors, monocytes/macrophages, fibrinogen, viscosity and cytokines that can impair microvascular perfusion (Hallenbeck JM 1994) Disruption of the blood brain barrier occurs in focal cerebral ischemia (the animal model of stroke) and the degree of the disruption correlates inversely with cerebral blood flow. (Yang GY & Betz, AL 1994) Free oxygen radicals have been shown to disrupt the blood brain barrier in focal ischemia which allows large molecules to pass through into the brain. Free radicals inhibit rather than cause postischemic hyperemia.(Tasdemiroglu E. et al 1994) which is one more mechanism that causes stagnation of blood flow through the ischemic penumbral zone. When blood flow is further reduced to approximately 15%, synaptic transmission is abolished (Branston, NM et al. 1977) (Heiss, WD et al 1976), extracellular potassium increases and ATP falls proportionately.. A massive release of extracellular potassium occurs at blood flow levels below 10%, ATP is totally exhausted, neurons depolarize, cellular ion homeostasis breaks down and cell death occurs.(Astrup,et al. 1977. (Welsh, F.A. et al. 1978) (Paschen, W et al 1992)
The margins of an infarct are usually strikingly irregular. The explanation for this probably lies in the preservation of the circulation in some limited areas through better anastomosis of collateral vessels. (W. Freeman 1933) (Tamura A. et al. 1981), (Tyson GW)
The debate about the size of the penumbra revolves around the methods used to study it. The morphological evidence is much less than the size shown by autoradiography (rat-Tyson et al 1984; cat-Ginsberg et al, 1976) and this area is much less than that shown by functional assessment (Symon et al., 1976). Substantial areas of flow reduction beyond the infarcted area(s) can be delineated by CT and MRI, while concurrently, oxygen utilization is decreased in these areas (Raynaud et al., 1987)(Benveniste H et al 1991). Repeat multitracer PET studies with human stroke victims have shown viable tissue in the border zone of ischemia up to 48 hours after the cerebrovascular attack. With few exceptions, these tissues suffer progressive metabolic derangement and had decreased cerebral metabolic rates of oxygen (-17.2% vs -26.1% as compared to normal mirror image regions of interests) within two weeks after the stroke. (WD Heiss et al. 1992). For many years cerebral ischemia has been thought to release glutamate from the hypoxic, damaged cells and this glutamate was thought to potentiate and propagate the initial hypoxic damage. Recently described, an alternative explanation for glutamate-mediated injury is hypoxia as well but caused by peri-infarct spreading depresssion-like depolarizations. These irregular depolarizations are thought to initiate or worsen hypoxic episodes (due to energy expenditures) and cause a further suppression in protein synthesis, a gradual deterioration in energy metabolism and a progression of irreversibly damaged tissue into the penumbra zone. Thus "interventions to improve ischemic resistance should therefor aim at improving the oxygen supply or reducing the metabolic workload in the penumbra region." (Hossmann KA 1994)
Focal cerebral ischemia is the animal model of stroke and in this model there is evidence for a reduction of the number of perfused capillaries in the affected penumbral areas. This loss of capillary perfusion is probably the result of a combination of changes that occur in the terminal capillary bed in the wake of the acute ischemic process. RBC aggregation, platelet aggregation, endothelial swelling, increased blood and plasma viscosity, etc are just some of the factors that contribute to the loss or decrease in the flow properties of red cells through ischemic tissue capillaries. Plasma, on the other hand, has been shown to reach all ischemic and post-ischemic capillaries and is able to pass through capillaries where red cells are no longer able to pass due to the constrictive and restrictive changes created by the ischemic process. (K.Kogure, K.A. Hossmann and B.K.Siesjo 1993) One of the mechanisms of action of hyperbaric oxygen is to increase the oxygen solubility in blood plasma. It is possible to dissolve sufficient oxygen (. i.e. 6 vol% in plasma) to meet the oxygen needs of the brain. (K.K.Jain, 1996) Thus in the acute stroke patient, the use of hyperbaric oxygen is able to provide oxygen to ischemic neurons and to keep them alive while either endogenous or exogenous fibrinolytic mechanisms are brought to bear on the cerebral thrombosis that is causing the ischemia. This results in the salvage of the ischemic penumbra to a degree impossible with any other therapy..
CHRONIC STROKE REHABILITATION
With the injury to the brain, blood vessels are damaged or destroyed. The tissue that surrounds the area of outright necrosis has had its circulation compromised and may be only receiving a fraction of the blood flow and oxygen that it needs for optimum health. Thus a disruption in structure creates immediately a change (decrease) in function. This decrease in function remains for months or years and the neurons in these areas are said to be in "hibernation" or "sleeping". Hyperbaric oxygen treatments when given daily stimulates a process called "angiogenesis" or the formation of new blood vessels. New blood vessels form in the vicinity of the damaged tissues as a result of certain chemical signals (e.g. angiogenin) that are produced by the newly re-energized neurons, endothelial cells and macrophages and are then secreted into the surrounding tissues. These signals stimulate new blood vessels which slowly reconnect to the damaged tissues and within 60 days of daily treatments, the "sleeping" neurons wake up and resume their normal functions as the proper structures return back in place. The hyperbaric oxygen induced blood vessel repair results in a permanent structural change in the blood vessels that re-supply the previously damaged and nonfunctioning nerve tissue which was occurring due to diminished and inadequate blood flow. These new blood vessels improve the blood flow and oxygen delivery to the damaged brain tissues and this results in permanent improvements in the stroke and traumatically brain injured person. Clinically, what you see is the return to life of a previously paralyzed and useless limb or limbs, improvement in swallowing, speech, thinking (cognition), memory, etc. Quite obviously not all of the disabilities disappear since there was a central core of dead tissue that can not be revived. However, after the two months of therapy, these people may continue to improve for at least two years after their treatment with hyperbaric oxygen especially if they continue with physical therapy. This all occurs in patients who may have not seen any improvement in their conditions for years after their stroke even with the use of any and all other therapies indicating that the brain’s milieu intérieur has been altered for the better since the neurons are able to slowly re-establish their lost connections in ways not possible before hyperbaric oxygen.
Outcome in stroke may be predicted to some degree by the volume of tissue affected. Comparative functional volume obtained by single photon emission computerized tomography (SPECT) often indicates a larger region of recoverable tissue than CT.(Mountz, JM 1990) This functional volume of the infarct size can be demonstrated to decrease after one to several hyperbaric oxygen treatments (Neubauer, 1990, 1992) and this increase in blood flow to the area of infarction that occurs as a result of hyperbaric oxygen can serve as a clinical test to determine if there is salvageable neurons still present in the penumbra. Presumably, if the test (SPECT first, then HBO then repeat SPECT) is positive, the person should receive benefit from the use of a series of hyperbaric oxygen treatments because of the revitalization of the ischemic penumbral tissues.
This is a good test if the test is positive since we are generally assurred that the person will experience improvement with hyperbaric oxygen. However, what if the test is negative? Since the literature and clinical experience predicts that between 80 to 90 percent of stroke victims will be helped by hyperbaric oxygen, perhaps the SPECT scan may be missing some other fundamental mechanism by which hyperbaric oxygen is helping these people improve. For example, when rat’s forebrains are made ischemic for 10 minutes and then after 1, 2, 3 weeks and 3 months their cerebral glucose utilization is measured, generalized reductions in glucose utilization is found throughout the majority of gray matter indicating that widespread alterations of functional activity prevail in postischemic brains beyond the selectively vulnerable regions. (Beck T, et al 1995) Following acute, localized lesions of the central nervous system, arising from any cause, there are immediate depressions of neuronal synaptic functions in other areas of the central nervous system remote from the lesion. These remote effects result from deafferentation, a phenomenon known as "diaschisis". (Von Monakow C. 1914)
After an interval of time, which will vary directly with the severity of the lesion, functional recovery may occur to some degree due to synaptic reactivation of neurons. This is favorably influenced by rehabilitation. Diaschisis most commonly manifests itself by such neurological signs as impaired consciosness or cognitive impairments including dementia, dyspraxias, dystaxias, dysphasias, incoordination and sensory neglect. The nature of diaschisis has been demonstrated by widespread depressions of local cerebral blood flow and metabolism extending far beyond the anatomical lesion. Von Monakow pointed out that development of diaschisis is enhanced by latent circulatory disorders in both the affected and unaffected areas of the brain. Recovery of function is associated with recovery of local perfusion and metabolism. (Meyer, JS,et al 1993)
More recently PET scans have shown that diaschisis does not independently add to the clinical deficit in human cerebral infarction but represents part of the damage done by the stroke. (Bowler JV et al. 1995) "Diaschisis is a functional phenomenon that correlates with both stroke severity and infarct hypoperfusion volume" (Infeld B; et al.1995)
In another PET scan study of 31 patients with infarcts involving the frontal sensorimotor cortex, 23 had persistent diaschisis up to 5 years after onset while the remaining 8 had the diaschisis recover without recovery of oxygen metabolism in the infarcted area (implying that tissue in the ischemic penumbra did recover and this is what allowed for recovery of the diaschisis). (Miuura H; et al.1994.)
Thus if functionless ischemic penumbral tissue can be "re-activated" and be made to function again, a coresponding amount of the areas of diaschisis will be returned to normal with normal blood flow and function returning.
In a number of studies in normal dogs, monkeys and Man, hyperbaric oxygen has been shown to diminish cerebral blood flow from 1 to 29% (average 14.7%) which some people have claimed to be detrimental to a stroke or brain injured patient. All of these studies were done in normal non-brain injured subjects while the studies that were done in brain injured patients all showed an increase in cerebral blood flow (Jain, 1996 page 239). Dr. K.K. Jain states, "Vasoconstriction and reduced cerebral blood flow do not produce any clinically observable effects in a healthy adult when pressures of 1.5 to 2 ATA are used. ..The effects of HBO are more pronounced in hypoxic/ischemic states of the brain. HBO reduces cerebral edema and improves the function of neurons rendered inactive by ischemia/hypoxia. The improvement of brain function is reflected by the improved electrical activity of the brain."
The following abstracts are many of the articles which document the effectiveness of hyperbaric oxygen for the treatment of stroke. The normal course of therapy which has been shown by numerous clinicians amd scientists consists of 60 treatments of from one to two hours per session. Our clinical experiences have demonstrated to us that sixty treatments of one and one half hours per day will result in the most rapid and complete recovery. In combination with hyperbaric oxygen, an intensive physical therapy program must be carried out as well in order to maximize the therapeutic benefits of both. Further documentation of the combination of hyperbaric oxygen and physical therapy may be found in chapter 17 of K.K. Jain’s 1996 book, "Textbook of Hyperbaric Medicine" published by Hogrefe and Huber ISBN 0-88937-127-X. To order call 1-206-820-1500 (P.O.Box 2487, Kirkland, WA 98083-2487). Retail price $128.00.
RESEARCH IN HYPERBARIC OXYGEN THERAPY AND STROKE
Akimov, G.A. et al. "Assessment of the Efficiency of Hyperbaric Oxygenation Therapy in Early Forms of Cerebrovascular Disorders."
NEUROSCI BEHAV PHYS, l985; 15: 13 - 16.
Abstract:
We present results of the assessment of the efficiency of hyperbaric oxygenation therapy in 104 patients with cerebrovascular diseases. Of these patients, 32 had chronic cerebrovascular insufficiency and 72 showed transient disturbances of the cerebral circulation. A good effect was noted in 74 patients, a satisfactory one in 22, and a doubtful one in 8 patients. It is concluded from clinical, electro-physiological, psychophysiological, biochemical, and ophthalmoscopic examinations that hyperbaric oxygenation therapy is quite efficient when used as part of a combined therapy and as a means of prompt therapy of acute cerebrovascular crises. Observations over three to five years of patients repeatedly receiving the hyperbaric oxygenation therapy at 6 month intervals allows us to recommend it for the prevention of cerebral strokes.
Hart, G.B. et al. "The Treatment of Cerebral Ischemia with Hyperbaric Oxygen (OHP)." STROKE, l971; 2: 247-250.
Abstract:
The treatment of a patient for three and one-half months, following occlusion of the right middle cerebral artery with the associated neurological sequelae, with hyperbaric oxygen combined with methyldopa and hydrochlorthazide is presented. Treatment scheduled was two and one-half atmospheres absolute. The treatment was interrupted after 15 treatments to rule out spontaneous remission for a period of 30 days, and no further improvement occurred until treatments were reinstituted. The dramatic return to a near normal state during treatment appears to indicate that he did benefit from therapy.
Heyman, A. et al. "The use of Hyperbaric Oxygenation in the Treatment of Cerebral Ischemia and Infarction." CIRCULATION, Supplement 2: May, l966; 20- 27.
Summary:
The therapeutic usefulness of hyperbaric oxygenation in cerebral vascular disease was evaluated in 22 persons with recent neurologic deficits caused by cerebral embolism, thrombosis, hemorrhage, or arteriographic complications. Hyperoxygenation produced a significant elevation in content and tension of oxygen in blood and increased the reservoir of oxygen available for utilization by neurons. Remarkable and dramatic improvement in neurologic function occurred in four patients. In two others the neurologic deficit recurred a few hours after removal from the hyperbaric chamber; repeated exposure to high oxygen pressures was associated with only temporary improvement. In six other patients there was some evidence of clinical recovery immediately after onset of hyperoxygenation, but the neurologic deficit returned during decompression. The remaining 12 patients did not improve during hyperbaric oxygenation.
These observations indicate that in some patients neuronal structures remain viable for some hours after loss of function in acute cerebral ischemia. In such instances an increase in oxygen delivery may reverse cellular ischemia and prevent death of cerebral tissues. Hyperbaric oxygenation may provide supportive therapy in some patients with acute cerebral ischemia, thereby permitting the removal of the occlusive lesion by surgery or other methods.
Holbach, K. H. et al. "Neurological and EEG Analytical Findings in the Treatment of Cerebral Infarction with Repetitive Hyperbaric Oxygenation."
PROCEEDINGS OF THE SIXTH INTERNATIONAL CONGRESS ON HYPERBARIC MEDICINE, Aug. 31 - Sept. 2, l979, University of Aberdeen, Aberdeen, Scotland, pp. 205-210; Ed. George Smith DSC, MD, Aberdeen University Press, l979.
"...These findings indicate that unilateral occlusion or stenosis of the internal carotid or middle cerebral artery can lead to distinct focal neurological deficits and EEG alterations as well as to bilateral reduction of cerebral function and EGA (electrical brain activity). It also appears that such ischemic alterations of the brain can be improved by HBO therapy not only in the acute but also in the chronic post-stroke stage. Accordingly, we feel that this mode of treatment may be considered as an additional measure in the management of stroke."
Holbach, K. H. et al. "Advantage of Using Hyperbaric Oxygenation (HO) in Combination with Extra-Intracranial Arterial Bypass (EIAB) in the Treatment of Completed Stroke." ACTA NEUROCHIRUGICA, Suppl 28: 309: l979.
"...The evaluation of the effect of HO treatment on post-stroke alterations of the brain can be helpful in differentiating between reversible and irreversible changes, and thus response to HBO treatment may be used as a criterion for the prognosis of the cerebrovascular lesion and also for selection of patients for EIAB surgery."
Holbach, K.H. et al. "Differentiation between Reversible and Irreversible Post-Stroke Changes in Brain Tissue: Its Relevance for Cerebrovascular Surgery." SURG. NEUROL., l977; 7: 325-331.
Abstract:
Thirty-five selected patients with chronic stroke were studied. They had internal carotid occlusion wiht considerable neurological deficit persisting for an average of ten weeks. First, hyperbaric oxygen treatment was administered to each patient. Subsequently extra-intracranial anastomosis operations were performed on 20 of these patients. These patients were divided into three groups. Group 1 - 15 of the 35 patients - showed a significant improvement of cerebral function at the conclusion fo the hyperbaric oxygen treatment. Subsequently an extra-intracranial anastomosis operation was carried out on each patient resulting in considerable further recovery of cerebral functions. Group II consisted of 15 patients who showed only little change in neurological deficit at the conclusion of hyperbaric oxygen therapy. Extra-intracranial anastomosis operations were not carried out in Group II. Group III consisted of five patients with little or no change at the conclusion of hyperbaric oxygen treatment. Subsequent extra-intracranial anastomosis operations were, however, performed in these five patients. Although post-operative angiography revealed considerable filling of the affected middle cerebral territory by the new collateral channel, there was little change in their status. These findings suggest that in the chronic post-stroke stage a) hyperbaric oxygen therapy can improve ischemic alterations of the brain, b) it may be helpful in differentiating between reversible and irreversible alterations of brain tissue, c) extra-intracranial anastomosis may result in additional recovery of impaired neurological functions in those patients who have shown significant improvement from hyperbaric oxygen therapy and d) response to hyperbaric oxygenation may be used as a criteria for selection of patients for cerebral revascularisation procedures.
Holbach, K.H. et al. "Reversibility of the Chronic Post-Stroke State." STROKE, l976; 7(3): 296-300.
Abstract:
Summary: Forty patients with cerebral infarction associated with occlusion of the internal carotid artery (ICA) or the middle cerebral artery (MCA) were treated with hyperbaric oxygenation (HO). EEG analysis were performed regularly in order to assess the course of the cerebral lesion. Patients in an early post-stroke stage (IIIB) and patients in a chronic post-stroke stage (IV) had the changes in EEG analysis and neurological findings distributed evenly between these two groups.
In 27% of the cases, the improvement was considerable, 53% had moderate improvement, and 20% showed no change of condition. The improvement mainly consisted of an increase in alpha-wave and beta-wave activity over the affected brain region. We were able to show this fact clearly by means of the EEG-analysis-system applied. The results show that (a) hyperbaric oxygenation therapy (HOT) has a very favorable influence upon the course of disease, and (b) simultaneous application of HOT and EEG analysis allows for a differentiation between reversible and irreversible post-stroke changes in brain tissue.
Jain, K. K. "Chapter 17: Role of Hyperbaric Oxygen Therapy in the Management of Stroke." pp. 227 - 252; in TEXTBOOK OF HYPERBARIC MEDICINE, Hogrefe & Huber Publishers, Lewiston, NY, l990.
"HBO therapy should be started in the acute phase of a stroke as an adjunct to conventional medical management. Rehabilitation of stroke patients should also be planned during the first few months following stroke. Long-term follow-up studies are required to determine whether such measures would reduce the chronic disability from stroke and reduce the incidence of severe spasticity in stroke patients. The use of HBO may also reduce the need for some surgical procedures."
Jain, K.K. et al. "Hyperbaric Oxygen Therapy in the Rehabilitation of Stroke Patients." 2nd EUROPEAN CONFERENCE ON HYPERBARIC MEDICINE, l990; Organized by the Foundation for Hyperbaric Medicine in Basel and the Department of Surgery of the University Clinic in Basil.
Abstract:
Summary: A 100% response rate was demonstrated in 25 patients in sub-acute and chronic post-stroke stage. In spite of medical management and physical therapy, these patients had shown no day-to-day changes in their neurological status. Increase of motor power of the paralysed hand was demonstrated by a dynamometer. The improvement was transient initially but was maintained following a course of daily treatments (1.5 ATA for 45 min.) for 6 weeks in most of the cases. There was also a significant reduction of spasticity during HBO treatment and this relief could be extended by instituting physical therapy in the chamber. In conclusion, we feel that HBO is a useful adjunctive treatment in the rehabilitation of stroke patients.
Jain, K. K., "Effect of Hyperbaric Oxygenation on Spasticity in Stroke Patients." J Hyperbaric Med, l989; 4(2): 55-61.
Abstract:
The effect of hyperbaric oxygenation (HBO) at 1.5 ATA on spasticity of stroke was observed in 21 patients undergoing rehabilitation. The patients served as their own controls. HBO reduced spasticity in all the patients, an effect that was more marked than that of physical therapy, hyperbaric air, or 100% normobaric air. Initially the effect was transient and subsided within 24 h after treatment, but by conducting physical therapy simultaneously with daily, 45 min HBO sessions, lasting results were achieved after 5 wks and could be maintained by physical therapy alone during the follow-up, which varied from 6 mo to 1 yr. The exact mechanism of relief of spasticity is not known but it is probably due to improvement of the function of neurons in the penumbra zone of the cerebral hemisphere affected by stroke. This concept is supported by documented improvement of cerebral metabolism, EEG, rCBF, and motor function in stroke patients after HBO therapy. From the available evidence, HBO is considered to be an invaluable adjunct in the rehabilitation of stroke patients with spastic hemiplegia. Although the effects were documented in the paralyzed limbs, spasticity improved in other groups of muscles as well.
Lebedev, V.V., et al. "Effect of Hyperbaric Oxygenation on the Clinical Course and Complications of the Acute Period of Ischemic Stroke." ZHURNAL VOPR NEIROKHIRNRY, l983; 3: 37-42.
Hyperbaric oxygenation (HBO) was included in the therapuetic complex for 124 patients in the acute stage of ischemic stroke. The effect of HBO on the clinical course was appraised by comparing the dynamics of changes in the clinical symptoms and the frequency of complications in patients exposed to HBO with those in the control group
(patients not exposed to HBO). It was established that the depth of unconsciousness and the motor and aphasic disorders decreased during a HBO session, but the effect was usually short-lived. Aggravation of the patients' condition in the first week of the disease, evidently caused by increase of cerebral edema, occurred much less frequently when HBO was included in the complex of therapeutic measures. The number of patients with regression of the neurological symptoms was practically the same with and without the use of HBO, but the regression of the neurological defects was most evident in patients exposed to HBO. HBO prevents the development of recurrent cerebral circulatory disorders in the acute stage of ischemic stroke and reduces the incidence of some complications in this period (pneumonia, pulmonary edema, thromboembolism of the pulmonary artery, etc).
Nighoghossian, N. et al. "Hyperbaric Oxygen in the Treatment of Acute Ischemic Stroke. A Double-blind Pilot Study." STROKE, l995; 26: 1369-1372.
Abstract:
Background and Purpose: The effects of hyperbaric oxygen (HBO) therapy on humans are uncertain. Our study aims first to outline the practical aspects and the safety of HBO treatment and then to evaluate the effect of HBO on long-term disability.
Methods: Patients who experienced middle cerebral artery occlusion and were seen within 24 hours of onset were randomized to receive either active (HBO) or sham (air) treatment. The HBO patients were exposed daily to 40 minutes at 1.5 atmospheres absolute for a total of 10. We used the Orgogozo scale to establish a pretreatment functional level. Changes in the Orgogozo scale score at 6 months and 1 year after therapy were used to assess the therapeutic efficacy of HBO. In addition, we used the Rankin scale and our own 10-point scale to assess long term-disability at 6 months and 1 year. Two sample t tests and 95% confidence intervals were used to compare the mean differences between the two treatment groups. Student's two-tailed test was used to compare the differences between pretherapeutic and posttherapeutic scores at 6 months and 1 year in the two treatment groups.
Results: Over the 3 years of study enrollment, 34 patients were randomized, 17 to hyperbaric treatment with air and 17 to hyperbaric treatment with 100% oxygen. There was no significant difference at inclusion between groups regarding age, time from stroke onset to randomization and Orgogozo scale.
Neurological deterioration occurred during the first week in 4 patients in the sham group, 3 of who died; this worsening was clearly related to the ischemic damage. Treatment was also ciscontinued for 3 patients in the HBO group who experienced myocardial infarction, a worsening related to the ischemic process, and claustrophobia. Therefore, 27 patients (13 in the sham group and 14 in the HBO group) completed a full course of therapy.
The mean score of the HBO group was significantly better on the Orogozo scale at 1 year. However, the difference at 1 year between pretherapeutic and posttherapeutic scoreswas not significantly different in the two groups. Moreover, no statistically significant improvement was observed in the HBO group at 6 months and 1 year according to Rankin score and our own 10-point scale.
Conclusions: Although the small number of patients in each group precludes any conclusion regarding the potential deleterious effect of HBO, we did not observe the major side effects usually related to HBO. Accordingly, it can be assumed that hyperbaric oxygen might be safe. We hypothesize that HBO might improve outcome after stroke, as we detected an outcome trend favoring HBO therapy. A large randomized trial might be required to address the efficacy of this therapy.
Neubauer, R.A. et al. "Hyperbaric Oxygen and Imaging Techniques in Diagnosis and Therapy of Stroke. Does the Ischemic Penumbra Alter the Outcome in Stroke?" INTERNATIONAL SYMPOSIUM: NEUROPSYCHOMOTOR, NEUROPHARMACOLOGICAL, PSYCHOSOCIAL AND ETHICAL ASPECTS, Oct. 7-11, l992; Siracusa, Italy.
Abstract:
Recovery from stroke (a global phenomena) and predictability of outcome may be directly related not only to tissue damage, but also the ischemic penumbra or surrounding zone of idling neurons. The local and global effects of stroke are well known. Actual recovery or evolution in the neuronal tissue may go on for months. All events related to recovery have yet to be elucidated. It is known that recovery of ischemic or hypoxic tissue is more related to the oxygen content than to blood flow. Utilization of Single Photon Emission Computerized Tomography (SPECT) with the radiotracer Iofetamine I123, aids in demonstrating ischemic penumbras (reperfusion amplitudes) in strokes, thus lending support to the work of Symon, Astrup and Holbach. SPECT analysis before and after a single exposure of hyperbaric oxygen at 1.5 ATA for 60 minutes was performed on 15 stroke patients with strokes ranging in time from 6 hours to 15 years. In all of these patients marked changes in flow and metabolism were seen after hyperbaric intervention, even in cases with neurologic defects present for up to 15 years. This causes speculation as to when stroke is really completed or fully evolved and whether the standard methods of treatment of stroke, and, by extension, all brain injury, encompass the full understanding of the hypoxic or ischemic penumbra. Five cases are presented here: 4 showed varying degrees of improvement associated with a viable halo zone. One patient demonstrated an absent ischemic penumbra. A new protocol combining HBO and surface oxygen will be suggested.
Neubauer, R. et al. "Enhancing idling neurons." letter. THE LANCET, March 3, l990; 542.
"After HBO there was a sharp increase in tracer uptake in areas showing hypometabolism on the pre-HBO study...Reduced spasticity, improved ambulation and speech, and cessation of drolling were noted."
Neubauer, R. et al. "Stroke Treatment." (letter). THE LANCET, June 29, l991; 1601.
"Hyperbaric oxygen (HBO) efficiently increases the diffusional driving force for oxygen, thereby increasing tissue oxygen availability. This overcomes ischemia/hypoxia and so reduces cerebral edema, restores integrity to the blood/brain barrier and cell membranes, neutralizes toxic amines, promotes phagocytosis, scavenges free radicals, stimulates angiogenesis, and reactivates idling neurons."
Neubauer, R. et al. "Delayed Metabolism or Reperfusion in Brain Imaging after Exposure to Hyperbaric Oxygenation - A Therapeutic Indicator?" PROCEEDINGS OF THE XV ANNUAL MEETING OF THE EUROPEAN UNDERSEA BIOMEDICAL SOCIETY, Sept. 17-21, l989; Eilat, Israel.
Abstract:
Single Photon Emission Computerized Tomography (SPECT) analysis with Iofetamine I123 was performed in patients with various Central Nervous System (CNS) dysfunctions before and after a single exposure to hyperbaric oxygen (1.5 ATA for 60 minutes) as a guide to potential therapeutic intervention. In CNS disorders current measurements had precluded the identification of idling neurons or the ischemic penumbra, as most techniques involved electrophysiological computerized data. Poorly functioning, yet viable cells, if not electrically active are not identifiable. These cells, however, given the proper oxygen/glucose ratio may return to normal function with dramatic results. Increased Iofetamine I-123 tracer uptake in these ischemic areas (idling neurons) after hyperbaric oxygen therapy probably reflects reactivation of hypometabolic neuronal tissue. Unlike MRI or CT, SPECT reflects regional blood flow as well as grey matter metabolism. The similarity to PET imaging is noteworthy. A variety of patients with central nervous system dysfunction were studied. Reactivation of marginal or idling neurons was seen in many disease entities, the most dramatic being long standing hypoxic encephalopathies. Demonstrative cases will be presented including hypoxic encephalopathy and acute and chronic neurologic deficit of stroke. Reactivation of the idling neuron may be of clinical significance. It is important for the physician to differentiate between viable and non-viable tissue, both from the standpoint of treatment and prognosis.
Neubauer, R.A. "Generalized small-vessel stenosis in the brain. A case History of a Patient Treated with Monoplace Hyperbaric Oxygen at 1.5 to 2 ATA." MINERVA MEDICA, l983; 74: 2051-2055.
Abstract:
Complete evaluation of older patients with mental changes always leaves us with a certain percentage whose condition can only be attributed to atherosclerosis. Little is being done for these patients because this generalized stenosis of the brain does not reverse with any known treatment. This writer has treated many such patients with hyperbaric oxygen (HBO), and presents this case history, along with regional cerebral blood flow (rCBF) studies, showing the type of changes which frequently occur. This case initially presented with symptoms of gross mental confusion, memory loss, both recent and remote, irrational speech and occasional violence. Although prior complete evaluations were concluded with no recommended treatment, the initial series of HBO treatment resulted in a well-functioning patient. This was maintained for four years with intermittent HBO. The patient then presented with acute stroke, total disorientation and confusion. He again became functional with HBO. A discussion of the mechanisms of HBO which might account for the changes is given.
Neubauer, R.A. et al. "Hyperbaric Oxygenation as an Adjunct Therapy in Strokes Due to Thrombosis." STROKE, l980; 11(3): 297-300.
Abstract:
Results are reported using hyperbaric oxygenation (HBO) in 122 patients with strokes due to thrombosis, both acute and completed. HBO is used as adjunctive treatment and there appears to be justification for a controlled study to delineate the treatment further. The authors believe it is essential to treat patients with stroke at 1.5 to 2 atmospheres absolute (ATA).
Marroni, A. et al. "Hyperbaric Oxygen Therapy at 1.5 or 2.0 ATA as an Adjunct to the Rehabilitation of Stabilized Stroke Patients. A Controlled Study." PROCEEDINGS OF THE 9th INTERNATIONAL CONGRESS ON HYPERBARIC MEDICINE, March 1-4, l987; Sydney, Australia.
Abstract:
HBO Therapy has been studied by many authors as an adjunctive treatment for stroke patients. Satisfactory results have been reported for the use of HBO as a predictive tool for EC-IC revascularization. The questions of the appropriate treatment pressure has been debated in the literature.
We studied a group of 80 well stabilized cerebral thrombosis patients not any more undergoing any form of treatment or care. Average age was 59.7 yrs., average stroke age 29.2 months. The patients were divided into 8 groups: A: control group not undergoing any care; B: in water rehabilitation, 30 sessions, no HBO; C1: 30 HBO sessions at 2.0 ATA; C2: same at 1.5 ATA; D1: HBO at 2 ATA plus rehabilitaiton as above; D2: same at 1.5 ATA; E1: HBO and simultaneous rehabilitation in our specially built Hyperbaric pool at 2 ATA; E2: same at 1.5 ATA.
The Rehabilitation protocol was originally developed at our Center as well as a quantitized and repeatable Neuromotor Disability Evaluation Scale. Patients were controlled prior to beginning, every 10 days during treatment, then 1 and 3 months after.
Obtained data show defined and similar HBO effects on the improvement of patients'
performance at 1.5 and 2.0 ATA, a clear and significant potentiation of this effect being evident for the Hyperbaric Rehabilitation groups and especially for the group treated at 2.0 ATA. The obtained results were still present at the third month after treatment.
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