Effect of Hyperbaric Oxygenation on Spasticity in Stroke Patients

Hyperbaric Healing Systems, Inc. and
Advanced Wound Care Systems, Inc.

Hope·Health·Healing

Effect of Hyperbaric Oxygenation on Spasticity in Stroke Patients

Jain K.K.
J Hyper. Med 4: 55-61, 1989
HBOT Relieves Muscle Spasticity After Stroke
HBOT brings permanent reduction of spasticity in stroke victims.

Hyperacute hyperbaric oxygen for CNS ischemia

R. A. Neubauer

Ocean Hyperbaric Center, Lauderdale-by-the-Sea, Florida

SUMMARY

Basically, there has been no specific treatment for the acute stroke with the exception of thrombolytic drugs. However, of the approximately 700,000 stroke patients in the United States, only about 6% receive thrombolysis. In the acute stroke it has been shown that the basic deficit is that of oxygen rather than blood flow (1). A recent communication in Lancet indicated that neuronal tissue may still act as an active transport 8 hours post mortem (2). In the acute stroke the logic and human and animal research for the use of pressurized oxygen is abundant. A communication in Lancet in 1991 described the ischemic cascade (3). It is obvious that hyperbaric oxygen would play a major role in limiting this cascade by helping to reduce cerebral edema, maintain the integrity of the blood barrier, protecting the cell membrane, oxygenating the mitochondria, as well as reducing lactate peaks and toxic amines. This evidence for the use of hyperbaric oxygen in the acute stroke resulted in an excellent meeting in Washington, D.C., May 9-14, 1998 regarding cerebral vascular ischemia, dementia, space and underwater medicine with a major thrust on advancing a protocol for the treatment of the acute ischemic thrombotic stroke. The discussion was enthusiastic and extremely scientific and a proposed protocol was devised for multi-center research to be presented for suggestion and criticism.

INTRODUCTION

The above, along with abundant animal research and certain human data suggests an immediate course of hyperbaric oxygen following the onset of stroke. Attempts to prove this have been published in the worldwide literature including studies by Nighossian (4), Heyman (5), Anderson (6) and others, including considerable work by the Russians (7). Critical aspects, however, were not met in these studies, those being A) the time of intervention, B) the appropriate pressure and the number and C) the frequency of treatments.

Lacking also was any type of sequential imaging to follow progress. Neubauer and End, however, in 1980, published data on stroke patients treated with hyperbaric oxygen within the first four hours of onset (8). A large percentage (25%) of such patients were discharged within 24 hours of hospitalization. The savings suggested are immense. This was the first paper to publish a specific protocol utilizing treatments of 1.5 to 2 ATA, one hour each, every 6 hours until the stroke was stabilized with a total of 10-20 treatments for every patient. Also noted in this original publication was the fact that the number of patients requiring nursing home care following stroke was statistically significantly reduced as compared to the control group. This paper has recently been revisited by a statistician and this data will be presented.

MATERIALS AND METHODS

Newer imaging techniques, particularly single photon emission computerized tomography (SPECT) and diffusion weighted MRI now allow a rapid and efficient visualization of brain function. These are similar to PET but are far less expensive and more readily available. We have been using a tracer Ceretec HM- PAO 99m which crosses the blood brain barrier and therefore measures not only blood flow but also metabolism. Our acute stroke protocol has been to obtain a baseline scan followed by one hour of hyperbaric oxygen (1.5 ATA) and then a repeat scan. Under these circumstances, a predictability of the outcome may be almost immediately available. In the acute stroke patient we have continued to follow the protocol published in 1980 with an extension past 20-40 treatments when necessary. We also incorporate into the treatment program all modalities of physical, occupational, speech -therapies, nutritional counseling and certain herbal products.

CASE REPORT

The images presented herein show the effect of a single hour of hyperbaric oxygen exposure on brain blood flow and, in all probability, metabolism. A case is presented with SPECT imaging before and after hyperbaric oxygen. A 74 year old white male patient experienced an acute onset of right-sided weakness and dizziness with slight confusion. Within three hours the patient had a SPECT scan with a split dose of Technetium 99 m HMPAO. A 1/4 dose was administered for the first scan and the patient was then given 1.5 ATA of oxygen in a hyperbaric chamber for 1 hour. The remaining 3/4 dose of Tc 99 m HMPAO was administered and scan was repeated after two hours. The baseline scan showed a marked reduction of perfusion in the area of the left middle cerebral artery with reduced perfusion in the left temporal lobe, the basal ganglia, the posterior occipital poles and throughout the lower gyre of the frontal lobes, worse on the left. The follow-up scan after hyperbaric oxygen showed marked improvement in perfusion and metabolism of the left mid-cerebral artery. The patient was therefore treated on an out-patient basis with 16 treatments of hyperbaric oxygen (one hour each, twice per day at 1.5 ATA). A repeat scan performed one and half months after final treatment showed a holding pattern with even further overall improvement. Only minimal necrologic deficits were noted. It must be noted that because the symptoms may have resolved within 24 hours this could be classified as a transient ischemic attack. However the use of a split dose of Te 99m HMPAO SPECT with hyperbaric oxygenation made it possible in this case to make rational prediction of the extent of his final recovery. If such a treatment were established for patients during the transient ischemic attack, or as an effective modality in stroke, hospitalization may be avoided, the outcome significantly improved and costs dramatically reduced.

DISCUSSION

More recent data now indicates that the use of hyperbaric oxygen will reduce the adhesiveness and the stickiness of the neutrophils and the endothelium. It has antiplatelet effects, along with the reduction and the global edema and ischemia associated with rapid reduction in lactate peaks also account for some of the major reasons that this should be a prime therapy. There is also a neuro-protector effect on cell plasticity and the blood brain barrier. Basically, the problem is lack of oxygen but multiple other types of therapy have been attempted, anywhere from calcium channel blockers to neuroprotectors to Lazaroids to steroids, of little avail.

This clinical results in the above case are almost identical to the patients treated in the pre-scanning arena. It is, however, now with the visualization, that predictability of recovery and endpoints may be achieved before hospital DRG expires. This is in contradiction to thrombolysis where the endpoint may be up to three months. It is further suggested that this technique be used before and after thrombolysis.

Summary of Proposed Pilot Study of Hyperbaric Treatment of Ischemic Stroke Victims.

Specific Aims:

To evaluate if hyperbaric treatment has a neuroprotective effect with a potential reduction in morbidity measured by sequential SPECT imaging. This effect will be evaluated after a single hyperbaric treatment, after a comprehensive 5-day/12-treatment protocol, and after a 3 month followup period. In addition, differences between groups in the volume of infarcted tissue at 3-months by CT scan will be assessed.

To assess if there is a decreasing efficacy of hyperbaric treatment to spare brain tissue with increasing time after onset of stroke symptoms.

To assess if the use of tPA is associated with a differential efficacy of hyperbaric treatment to spare brain tissue.

To gather initial data on the impact of hyperbaric therapy on clinical outcome, survival (composite functioning scales (SSS, Barthel, Rankin), and development of subsequent stroke.

Eligibility:

To assess logistic challenges and patient acceptability of hyperbaric treatment.

Inclusion:
Incident (first) ischemic stroke patients with a baseline NIH stroke scale of at least 13.

Exclusions:

patients unable to be treated with hyperbaric oxygen therapy in less than 24 hours.

age less than 45.

pulmonary disease that would contraindicate hyperbaric treatment (i.e., severe emphysema, evidence of blobs requires chest x-ray, etc).

unstable medical conditions requiring immediate access (cardiac arrhythmia congestive heart failure, etc.

life- threatening diseases limiting likelihood of evaluation of study outcome or life expectancy below 3 months.

Initial Evaluation: A CT will be performed at admission to rule out hemorrhage (required for tPA treatment also). For patients reaching the hospital within the time window to permit tPA treatment, the administration of tPA will be completed prior to the initiation of the hyperbaric study protocol. However, once the tPA has been administered, these patients will be screened for eligibility and if eligible, offered the hyperbaric protocol. Patients who refuse tPA, as well as those with a hospital admission outside of the tPA window, can proceed directly to the hyperbaric protocol.

As part of the eligibility work-up, prior to randomization, a SPECT scan and a baseline standardized neurological exam (activities of daily living scales and NIH stroke scale) will be performed.

Treatment Evaluation: Patients will be randomized to receive hyperbaric therapy plus best medical therapy versus best medical therapy alone. The initial hyperbaric therapy will be performed (1.5 ATA for 60 minutes) in those randomized to treatment. In all patients, a second SPECT scan and NIH stroke scale will be performed 3 hours after randomization (i.e., after the initial treatment for those randomized to treatment, and at a similar time among those randomized to best treatment.)

For those randomized to hyperbaric therapy, follow-up treatments (1.5 ATA for 60 minutes) will be performed at 8-hour intervals (2 per day) for the following three days. Hence, there is a total of 5 days of treatment incorporating 12 treatments. At the end of each day an NIH stroke scale will be performed for all patients. At the end of the 5 day treatment period discharge, a second SPECT scan, NIH stroke scale, and the activities of living scales will be performed in all patients. At three months, patients will return for a clinic visit, where a SPECT scan, a CT scan, the NIH stroke scale and evaluation of activities of daily living will be repeated.

Analysis and Evaluation: Analysis will employ an intention-to-treat approach to assess differences in the volume measures from the SPECT scans, using a random-effect linear modeling approach. Differences in the efficacy at the follow-up times, the differential role of HBOT in tPA versus non-tPA patients, and the potential affect modification of demographic and risk factors will be assessed as interaction terms in these same models. The assessment differences in a composite score from the activities of daily living scales will use a similar approach, while time to subsequent stroke will use standard time-to- event analysis approaches. The sample size has not yet been determined.

Congress on Cerebral Ischemia, Vascular Demential, Epilepsy and CNS Injury.
New
Aspects of Prevention and Treatment from Space and Underwater Explorations.
World Federation of Neurology
May9-13, 1998
Washington, D.C., US.
Prepared by Drs. George and Virginia Howard - Statisticians

Astrup, Siesjo BK, Symon L. Thresholds of ischemia; the ischemic penumbra. Stroke 1981; 12: 723725.

Dai J. Swaab DF, Buijs RAM. Recovery of axonal transport in "dead neurons". Lancet 1998; 351: 500.

Editorial. Treatment for stroke?. Lancet 1991; 337: 1129-1131.

Nighoghossian N. Trouillas P. Adeleine P. Salford F. Hyperbaric oxygen in the treatment of the acute ischemic stroke. A double-blind pilot study. Stroke 1995; 26(8): 1369-1372.

Heyman A., et al. The use of hyperbaric oxygenation in the treatment of cerebral ischemia and infarction. Circulation, Supplement 2: May, 1966; (33-34): 20-27.

Anderson D, et al. A pilot study of hyperbaric oxygen in the treatment of human stroke. Stroke 1991; 22: 1137-1142.

Kazantseva NV, Makarova LD, Kabanov M, et al. Clinical effects of mechanisms of action of higher pressure in treatment of stroke. European J. Neurology June 1, 1997; 4, Suppl 1: 190.

Neubauer RA, End E. Hyperbaric oxygenation as an adjunct therapy in strokes due to thrombosis. A review of 122 patients. Stroke 1980; 11 (3): 297-300.

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