BackgroundTraumatic brain injury (TBI) is the leading cause of death and disability in the US. Approximately 70-90% of the TBI cases are classified as mild, and up to 25% of them will not recover and suffer chronic neurocognitive impairments. The main pathology in these cases involves diffuse brain injuries, which are hard to detect by anatomical imaging yet noticeable in metabolic imaging. The current study tested the effectiveness of Hyperbaric Oxygen Therapy (HBOT) in improving brain function and quality of life in mTBI patients suffering chronic neurocognitive impairments.Methods and FindingsThe trial population included 56 mTBI patients 1–5 years after injury with prolonged post-concussion syndrome (PCS). The HBOT effect was evaluated by means of prospective, randomized, crossover controlled trial: the patients were randomly assigned to treated or crossover groups. Patients in the treated group were evaluated at baseline and following 40 HBOT sessions; patients in the crossover group were evaluated three times: at baseline, following a 2-month control period of no treatment, and following subsequent 2-months of 40 HBOT sessions. The HBOT protocol included 40 treatment sessions (5 days/week), 60 minutes each, with 100% oxygen at 1.5 ATA. “Mindstreams” was used for cognitive evaluations, quality of life (QOL) was evaluated by the EQ-5D, and changes in brain activity were assessed by SPECT imaging. Significant improvements were demonstrated in cognitive function and QOL in both groups following HBOT but no significant improvement was observed following the control period. SPECT imaging revealed elevated brain activity in good agreement with the cognitive improvements.ConclusionsHBOT can induce neuroplasticity leading to repair of chronically impaired brain functions and improved quality of life in mTBI patients with prolonged PCS at late chronic stage.Trial RegistrationClinicalTrials.gov NCT00715052

BackgroundRecovery after stroke correlates with non-active (stunned) brain regions, which may persist for years. The current study aimed to evaluate whether increasing the level of dissolved oxygen by Hyperbaric Oxygen Therapy (HBOT) could activate neuroplasticity in patients with chronic neurologic deficiencies due to stroke.Methods and FindingsA prospective, randomized, controlled trial including 74 patients (15 were excluded). All participants suffered a stroke 6–36 months prior to inclusion and had at least one motor dysfunction. After inclusion, patients were randomly assigned to "treated" or "cross" groups. Brain activity was assessed by SPECT imaging; neurologic functions were evaluated by NIHSS, ADL, and life quality. Patients in the treated group were evaluated twice: at baseline and after 40 HBOT sessions. Patients in the cross group were evaluated three times: at baseline, after a 2-month control period of no treatment, and after subsequent 2-months of 40 HBOT sessions. HBOT protocol: Two months of 40 sessions (5 days/week), 90 minutes each, 100% oxygen at 2 ATA. We found that the neurological functions and life quality of all patients in both groups were significantly improved following the HBOT sessions while no improvement was found during the control period of the patients in the cross group. Results of SPECT imaging were well correlated with clinical improvement. Elevated brain activity was detected mostly in regions of live cells (as confirmed by CT) with low activity (based on SPECT) – regions of noticeable discrepancy between anatomy and physiology.ConclusionsThe results indicate that HBOT can lead to significant neurological improvements in post stroke patients even at chronic late stages. The observed clinical improvements imply that neuroplasticity can still be activated long after damage onset in regions where there is a brain SPECT/CT (anatomy/physiology) mismatch.Trial RegistrationClinicalTrials.gov NCT00715897

BackgroundFibromyalgia Syndrome (FMS) is a persistent and debilitating disorder estimated to impair the quality of life of 2–4% of the population, with 9:1 female-to-male incidence ratio. FMS is an important representative example of central nervous system sensitization and is associated with abnormal brain activity. Key symptoms include chronic widespread pain, allodynia and diffuse tenderness, along with fatigue and sleep disturbance. The syndrome is still elusive and refractory. The goal of this study was to evaluate the effect of hyperbaric oxygen therapy (HBOT) on symptoms and brain activity in FMS.Methods and FindingsA prospective, active control, crossover clinical trial. Patients were randomly assigned to treated and crossover groups: The treated group patients were evaluated at baseline and after HBOT. Patients in the crossover-control group were evaluated three times: baseline, after a control period of no treatment, and after HBOT. Evaluations consisted of physical examination, including tender point count and pain threshold, extensive evaluation of quality of life, and single photon emission computed tomography (SPECT) imaging for evaluation of brain activity. The HBOT protocol comprised 40 sessions, 5 days/week, 90 minutes, 100% oxygen at 2ATA. Sixty female patients were included, aged 21–67 years and diagnosed with FMS at least 2 years earlier. HBOT in both groups led to significant amelioration of all FMS symptoms, with significant improvement in life quality. Analysis of SPECT imaging revealed rectification of the abnormal brain activity: decrease of the hyperactivity mainly in the posterior region and elevation of the reduced activity mainly in frontal areas. No improvement in any of the parameters was observed following the control period.ConclusionsThe study provides evidence that HBOT can improve the symptoms and life quality of FMS patients. Moreover, it shows that HBOT can induce neuroplasticity and significantly rectify abnormal brain activity in pain related areas of FMS patients.Trial RegistrationClinicalTrials.gov NCT01827683

Background: Fibromyalgia syndrome (FMS), a condition considered to represent a prototype of central sensitization syndrome, can be induced by different triggers including childhood sexual abuse (CSA). Recent studies have demonstrated hyperbaric oxygen therapy (HBOT) can induce neuroplasticity and improve clinical outcome of FMS. The aim of the current study was to evaluate the effect of HBOT on patients suffering from FMS with a history of CSA.Materials and methods: A prospective randomized clinical trial conducted between July 2015 and November 2017 included women with a history of CSA who fulfilled fibromyalgia diagnosis criteria for at least 5 years prior to inclusion. Included participants (N = 30) were randomly assigned to treatment group, treated with 60 HBOT sessions and a control/crossover group received psychotherapy. After the control period, the control/crossover group was crossed to HBOT. Clinical outcomes were assessed using FMS questioners, post-traumatic stress disorder (PTSD) questioners and quality of life questioners. Objective outcome were assessed using brain function and structure imaging.Findings: Following HBOT, there was a significant improvement in all FMS questionnaires (widespread pain index, Fibromyalgia symptoms severity scale, Fibromyalgia functional impairment), most domains of quality of life, PTSD symptoms and psychological distress. The same significant improvements were demonstrated in the control following crossover to HBOT. Following HBOT, brain SPECT imaging demonstrated significant increase in brain activity in the prefrontal cortex, orbital frontal cortex, and subgenual area (p < 0.05). Brain microstructure improvement was seen by MRI-DTI in the anterior thalamic radiation (p = 0.0001), left Insula (p = 0.001), and the right Thalamus (p = 0.001).Conclusion: HBOT induced significant clinical improvement that correlates with improved brain functionality and brain microstructure in CSA related FMS patients.Trial Registration: www.Clinicaltrials.gov, identifier: NCT03376269. url: https://clinicaltrials.gov/show/NCT03376269

PurposeIschemic retinal damage can be reversed by hyperbaric oxygen therapy (HBOT) as long as irreversible infarction damage has not developed. However, the time window till irreversible damage develops is still unknown. The study aim was to evaluate the effect of HBOT and determine possible markers for irreversible retinal damage.Materials and methodsRetrospective analysis of 225 patients treated with HBOT for central retinal artery occlusion (CRAO) in 1999–2015. One hundred and twenty-eight patients fulfilled inclusion/exclusion criteria: age >18 years, symptoms <20 hours, and best-corrected visual acuity (BCVA) <0.5 logMAR.ResultsTime delay from symptoms to treatment was 7.8±3.8 hours. The BCVA was significantly improved after HBOT, from 2.14±0.50 to 1.61±0.78 (P<0.0001). The proportion of patients with clinically meaningful visual improvement was significantly higher in patients without cherry-red spot (CRS) compared to patients with CRS at presentation (86.0% vs 57.6%, P<0.0001). The percentage of patients with final BCVA better than 1.0 was also significantly higher in patients without CRS vs patients with CRS at presentation (61.0% vs 7.1%, P<0.0001). There was no correlation between CRS and the time from symptoms. HBOT was found to be safe, and only 5.5% of patients had minor, reversible, adverse events.ConclusionHBOT is an effective treatment for non-arteritic CRAO as long as CRS has not formed. The fundus findings, rather than the time delay, should be used as a marker for irreversible damage.