Hyperbaric oxygen therapy can improve post concussion syndrome years after mild traumatic brain injury - randomized prospective trial

Abstract

Background: Traumatic 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 findings: The 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.

Conclusions: HBOT 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 registration: ClinicalTrials.gov NCT00715052.

Figure 1. Flow chart of the patients in the study.

Figure 2. Assessment of the cognitive indices.

Each patient in each group was assigned a score at baseline, after the control period (for patients in the crossover group) and after HBOT. The figures show the mean scores and standard errors for the two groups at each stage for the four cognitive indices - Information Processing Speed (A), Attention (B), Memory (C) and Executive Functions (D), as defined in the method section.

Figure 3. Assessments of the general cognitive score.

The figure shows the level of the general cognitive score (defined in the text) for the crossover group at baseline, after the control period and after HBOT, and for the treated group at baseline and after HBOT.

Figure 4. Assessment of the relative changes.

A) The relative changes (as defined in the text) for the four cognitive indices. The changes are shown for the crossover group following the control period (green bars) and HBOT (blue bars), and for the treated group following HBOT (red bars). B) Relative changes in the general cognitive score for the same three cases as in (A).

Figure 5. Scatter plot analysis of the changes in cognitive indices.

The scatter plots show the normalized relative changes (NRC) as defined in the methods section and explained in the text above. A) Scatter plot for the changes in IPS as function of changes in EF. B) Scatter plot for changes in Attention as function of Memory. The changes in the Attention and in the IPS as function of the General cognitive score are shown in (C) and (D), respectively. Circles are for the treated group and diamonds are for the crossover group. The color code is: Red for changes during HBOT and blue for changes during control.

Figure 6. Assessments of the mean relative changes and standard errors in quality of life measurements.

The changes are shown for the crossover group following control period (green bars) and following HBOT (blue bars), and for the treated group following HBOT (red bars). Note that, according to the questionnaire structure, in the EQ-5D measurement improvement is reflected as score decrease, hence the negative values of change.

Figure 7. Distribution of the Brodmann areas relative SPECT CBF changes.

The change for each BA represents and averaging of the relative changes of all the patients as explained in the text. The results show a clear difference between the control and the HBOT periods. We note that the higher variations for the control period are associated with the fact that the averaging in this case is over 24 patients (the crossover group), while for the HBOT period the averaging is over all 55 patients.

Figure 8. Volume rendered Brain SPECT perfusion maps of Example 1, a 51-year-old woman from the treated group suffering mTBI that had occurred 2 years prior to inclusion in the study.

Comparison of the baseline activity (upper row) with the post HBOT activity (middle row) and the CBF changes (bottom row) demonstrated significant improvements after HBOT in bilateral orbito-frontal and lateral-parietal regions and left ventro-lateral-frontal region correlating to BAs 45, 47, and 11.

Figure 9. Volume rendered Brain SPECT perfusion maps of Example 2.

The results are of a patient in the treated group, suffering mTBI that had occurred 1 year prior to inclusion in the study. Comparison of the baseline activity (upper row) with the post-HBOT activity (middle row) and the CBF changes (bottom row) demonstrated significant improvements after HBOT in bilateral orbito-frontal regions, the medial aspect of the temporal lobes and the temporal poles that correspond to BAs 11, 25, 27, 28 and 38.

Figure 10. Volume rendered Brain SPECT images representing the percentage of CBF change post control period and post HBOT of the cross group patient described in example 3.

As can be clearly seen, the improvement in perfusion following HBOT was significantly high in most areas of the brain as opposed to insignificant change following the control period. The most significant improvements were in both frontal and temporal lobes and right parietal lobe.

Figure 11. Volume rendered Brain SPECT images representing the CBF change (in percentage) post control period and post HBOT of the cross group patient described in example 4.

The overall changes after the control period and the HBOT show normal variations of brain perfusion in the -10% to +10% range (from green to orange colors). However, close inspection reveals localized significant changes (white circles) in the in the right temporal pole and in the right dorso-lateral area. These changes in perfusion are in good agreement with the improvements in the cognitive indices as the SPECT detected changes correspond to Brodmann areas 45–46, 11, 38 and 39.