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A phase I study of low-pressure hyperbaric oxygen therapy for blast-induced post-concussion syndrome and post-traumatic stress disorder.

This is a preliminary report on the safety and efficacy of 1.5 ATA hyperbaric oxygen therapy (HBOT) in military subjects with chronic blast-induced mild to moderate traumatic brain injury (TBI)/post-concussion syndrome (PCS) and post-traumatic stress disorder (PTSD). Sixteen military subjects received 40 1.5 ATA/60 min HBOT sessions in 30 days. Symptoms, physical and neurological exams, SPECT brain imaging, and neuropsychological and psychological testing were completed before and within 1 week after treatment. Subjects experienced reversible middle ear barotrauma (5), transient deterioration in symptoms (4), and reversible bronchospasm (1); one subject withdrew. Post-treatment testing demonstrated significant improvement in: symptoms, neurological exam, full-scale IQ (+14.8 points; p<0.001), WMS IV Delayed Memory (p=0.026), WMS-IV Working Memory (p=0.003), Stroop Test (p<0.001), TOVA Impulsivity (p=0.041), TOVA Variability (p=0.045), Grooved Pegboard (p=0.028), PCS symptoms (Rivermead PCSQ: p=0.0002), PTSD symptoms (PCL-M: p<0.001), depression (PHQ-9: p<0.001), anxiety (GAD-7: p=0.007), quality of life (MPQoL: p=0.003), and self-report of percent of normal (p<0.001), SPECT coefficient of variation in all white matter and some gray matter ROIs after the first HBOT, and in half of white matter ROIs after 40 HBOT sessions, and SPECT statistical parametric mapping analysis (diffuse improvements in regional cerebral blood flow after 1 and 40 HBOT sessions). Forty 1.5 ATA HBOT sessions in 1 month was safe in a military cohort with chronic blast-induced PCS and PTSD. Significant improvements occurred in symptoms, abnormal physical exam findings, cognitive testing, and quality-of-life measurements, with concomitant significant improvements in SPECT.

Hyperbaric oxygen therapy improves spatial learning and memory in a rat model of chronic traumatic brain injury

In the present experiment we use a rat model of traumatic brain injury to evaluate the ability of low-pressure hyperbaric oxygen therapy (HBOT) to improve behavioral and neurobiological outcomes. The study employed an adaptation of the focal cortical contusion model. 64 Male Long-Evans rats received unilateral cortical contusion and were tested in the Morris Water Task (MWT) 31-33 days post injury. Rats were divided into three groups: an untreated control group (N=22), an HBOT treatment group (N=19) and a sham-treated normobaric air group (N=23). The HBOT group received 80 bid, 7 days/week 1.5 ATA/90-min HBOTs and the sham-treated normobaric air group the identical schedule of air treatments using a sham hyperbaric pressurization. All rats were subsequently retested in the MWT. After testing all rats were euthanized. Blood vessel density was measured bilaterally in hippocampus using a diaminobenzadine stain and was correlated with MWT performance. HBOT caused an increase in vascular density in the injured hippocampus (p<0.001) and an associated improvement in spatial learning (p<0.001) compared to the control groups. The increased vascular density and improved MWT in the HBOT group were highly correlated (p<0.001). In conclusion, a 40-day series of 80 low-pressure HBOTs caused an increase in contused hippocampus vascular density and an associated improvement in cognitive function. These findings reaffirm the clinical experience of HBOT-treated patients with chronic traumatic brain injury.

Decompression illness in divers: a review of the literature.

BACKGROUND–Neurologists may be consulted to diagnose and treat the severe neurologic injuries that can occur in divers with decompression illness (DCI). REVIEW SUMMARY–Subclinical bubbles form during normal diving activity. DCI, a diffuse and multifocal process, results when bubbles cause symptoms by exerting mass effect in tissues, or obstructing venous or arterial flow. The lower thoracic spinal cord is a commonly affected area of the central nervous system. The most commonly described form of brain DCI is cerebral arterial gas embolism with middle cerebral artery or vertebrobasilar distribution involvement. Bubbles exert secondary damage to the vascular endothelium, causing activation of numerous biochemical cascades. CONCLUSIONS–Divers can develop DCI on very short dives or in shallow water, even when adhering to protocols. DCI should be strongly considered when divers experience pain after diving. Any neurologic symptoms after a dive are abnormal and should be attributed to DCI. Even doubtful cases should be treated immediately with hyperbaric oxygen (HBO), after a chest x-ray to rule out pneumothorax. The Divers Alert Network should be contacted for emergency consultation. Delay to treatment can worsen outcome; however, the overwhelming majority of divers respond to HBO even days to weeks after injury. Although DCI is a clinical diagnosis, magnetic resonance imaging, somatosensory evoked potentials, single-photon emission tomography, and neuropsychologic testing help to document disease and monitor response to therapy. Divers should be treated with HBO until they reach a clinical plateau. Complete relief of symptoms occurs in 50% to 70% of divers; 30% have partial relief.

Low pressure hyperbaric oxygen therapy and SPECT brain imaging in the treatment of blast-induced chronic traumatic brain injury (post-concussion syndrome) and post traumatic stress disorder: a case report.

A 25-year-old male military veteran presented with diagnoses of post concussion syndrome and post traumatic stress disorder three years after loss of consciousness from an explosion in combat. The patient underwent single photon emission computed tomography brain blood flow imaging before and after a block of thirty-nine 1.5 atmospheres absolute hyperbaric oxygen treatments. The patient experienced a permanent marked improvement in his post-concussive symptoms, physical exam findings, and brain blood flow. In addition, he experienced a complete resolution of post-traumatic stress disorder symptoms. After treatment he became and has remained employed for eight consecutive months. This case suggests a novel treatment for the combined diagnoses of blast-induced post-concussion syndrome and post-traumatic stress disorder.A 25-year-old male military veteran presented with diagnoses of post concussion syndrome and post traumatic stress disorder three years after loss of consciousness from an explosion in combat. The patient underwent single photon emission computed tomography brain blood flow imaging before and after a block of thirty-nine 1.5 atmospheres absolute hyperbaric oxygen treatments. The patient experienced a permanent marked improvement in his post-concussive symptoms, physical exam findings, and brain blood flow. In addition, he experienced a complete resolution of post-traumatic stress disorder symptoms. After treatment he became and has remained employed for eight consecutive months. This case suggests a novel treatment for the combined diagnoses of blast-induced post-concussion syndrome and post-traumatic stress disorder.

Hyperbaric Oxygen Therapy for Post-Concussion Syndrome: Contradictory Conclusions from a Study Mischaracterized as Sham-Controlled

Dear Editor, The recent study by Wolf and associates has affirmed the effectiveness of hyperbaric (oxygen) therapy in the treatment of patients with mild traumatic brain injury (mTBI)/post-concussion syndrome (PCS) and post-traumatic stress disorder (PTSD). This affirmation emerges from analysis of the study data, rather than from the study’s stated conclusions. Mischaracterized as a shamcontrolled (placebo implied) design, the study errs in concluding that ‘‘HBO2 at 2.4 ATA pressure had no effect on post-concussive symptoms after mild TBI.’’ A reconsideration of the science of hyperbaric therapy reveals that the study by Wolf and colleagues is neither a sham nor placebo-controlled study. Rather, it is a Phase II study of two composite doses of hyperbaric therapy that demonstrated significant improvements in PCS and PTSD symptoms at the 2.4 atmospheres absolute (ATA) pure oxygen dose as well as the low-pressure 1.3 ATA air/oxygen dose. Hyperbaric (oxygen) therapy (HBOT) is a combination product of increased pressure and increased pressure of oxygen above ambient atmospheric pressure, according to scientific principles and current Food and Drug Administration understanding. Although traditionally misdefined as a treatment for diseases based on the increased oxygen component alone ( > 1.4 ATA oxygen), it is a treatment with hyperbaric pressure and hyperoxia for disease processes whose primary targets are oxygen and pressure sensitive genes. Evidence for this dual component nature of hyperbaric therapy is found in the 351-year history of hyperbaric air therapy and the recent 60-year history of animal, human tissue, and human experiments that have documented biological effects of pressure, especially in the micropressure range of the Wolf and coworkers ‘‘sham’’ control group and the control groups of the Department of Defense (DoD) HBOT TBI studies. Examples of this literature are listed in Tables 1 and 2. Pressures from 1.21–1.26 ATA delivered to human and 1.0015–1.015 ATA to animal endothelial cells, and 1.10 and 1.20 ATA to human platelets for 15 min or longer have caused the elaboration or suppression of vasoactive substances, and the elaboration of growth factors, inflammatory mediators, oxidation products, and cell proliferation. This literature and biological effects from a 1-min exposure to 1.09 ATA or 3 min at 1.04 ATA inform the symptomatic improvements noted in the Wolf and associates ‘‘sham’’ group, as do benefits of hyperbaric air on spinal function and PTSD in spinal cord injured veterans during a SCUBA diving training course. To meet the definition of a true sham, any controlled experiment to test HBOT must omit in its control groups the active ingredients of increased pressure and hyperoxia. The Wolf and colleagues ‘‘sham’’ control group does neither; rather, it includes both. The ‘‘sham’’ control group is exposed to 1.3/1.2 ATA of air, which is a 20–30% increase in pressure and 28–43% increase in plasma oxygen over sea level plasma oxygen and a slightly greater increase over San Antonio (hyperbaric treatment site) atmospheric pressure. Because pressure and hyperoxia are noninert—i.e., are biologically active—the Wolf and coworkers ‘‘sham’’ control group cannot test for placebo effects; placebo/ placebo response is defined as ‘‘The effect that an inactive or inert substance has on a clinical condition.’’ Wolf and associates allude to possible bioactivity of the control group, but the lack of discussion indicates a lack of appreciation that the presence of hyperoxia and pressure negate Wolf and colleagues characterization as a ‘‘sham’’ control group. Restating the design of the Wolf and coworkers study, it is a Phase II comparative dosing study of two composite doses of hyperbaric therapy (four actual doses), compressed air (low dose increased pressure and increased oxygen), and compressed oxygen (high dose pressure and high dose oxygen). Both doses were efficacious in the treatment of mTBI PCS and PTSD. The PTSD data demonstrated 18% and 22% reductions in the PCL-M (interpolated from the Figure 1 graph in Wolf and colleagues) in the HBOT and ‘‘sham’’ groups, respectively, after 30 2 h treatments. These reductions compared favorably with five other therapies/six studies for PTSD that used the PCL-M (6–45% reductions). The PCS ImPACT data were similarly significantly improved in both groups, but it is the disparity in component and pattern change on the ImPACT results for the two groups that underscore the dual dose design of the study and efficacy of these two doses: 10 IMPACT scores significantly improved in the low dose group compared with 2 in the high dose group. For all 22 items of the ImPACT, 20 improved, 1 was unchanged, and 1 was worse in the

Hyperbaric oxygen improves rate of return of spontaneous circulation after prolonged normothermic porcine cardiopulmonary arrest

AIM This controlled, prospective, randomized porcine study tests the hypothesis that high-dose hyperbaric oxygen (HDHBO2) compared with normobaric oxygen (NBO2) or standard-dose hyperbaric oxygen (SDHBO2), improves return of sustained spontaneous circulation (ROSC) after a normothermic, normobaric, 25-min, non-intervened-upon cardiopulmonary arrest. The study incorporated a direct mechanical ventricular assist device (DMVAD) for open chest continuous cardiac compressions (OCCC) to assist advanced cardiac life support (ACLS). The experiment demonstrates a dose response to oxygen concentration in the breathing mix used in resuscitative ventilation. MATERIALS AND METHODS Male pigs (average 30kg weight) underwent a 25-min, normothermic, non-intervened-upon cardiopulmonary arrest. Following arrest all animals were ventilated with 100% oxygen and were subjected to OCCC, incorporating DMVAD-aided ACLS. The animals so treated were randomized to be in one of three groups, with six animals in each group. The NBO2 group remained at 1.0 atmosphere absolute (ATA), while the SDHBO2 and HDHBO2 groups were initially placed at 1.9 and 4.0ATA, respectively. Uniform, but not American Heart Association (AHA) protocol, ACLS was maintained as needed over the ensuing 2h for all animals in all groups. At the end of 2h, the animals were euthanized. RESULTS Continuously sustained ROSC (mean arterial pressure > or =50mmHg at all times), without the need of the pump assist over the 2-h resuscitation attempt that followed the 25-min arrest, occurred in four out of six animals in the HDHBO2 group, and in none of the animals in the NBO2 or SBHBO2 groups (p< or =0.001). CONCLUSIONS Our results show significantly sustained ROSC using HDHBO2 to resuscitate swine after a 25-min, non-intervened-upon, normothermic cardiopulmonary arrest. These results could not be achieved using NBO2 or SDHBO2.

HBO Therapy in Global Cerebral Ischemia/Anoxia and Coma

Hyperbaric oxygen (HBO) therapy has been used in a number of conditions characterized by global ischemia (as opposed to focal ischemia of stroke), and anoxia, and leading to impairment of consciousness. Conditions such as coma due to brain injury and anoxia associated with drowning and hanging are discussed under the following headings: (1) pathophysiology, (2) rational basis of HBO therapy, (3) review of animal experimental studies, and (4) review of human clinical studies. Finally case studies are given.