Search

Background: Some clinical trials report improvement in persistent post-concussive symptoms (PCS) with hyperbaric oxygen (HBO2) following mild traumatic brain injury (mTBI), but questions remain regarding the utility of HBO2 for PCS, the effects of HBO2 on post-traumatic stress disorder (PTSD), and the influences of sham control exposures. Methods: A systematic review and pooled analysis was conducted to summarize available evidence for HBO2 in mTBI-associated PCS ± PTSD. Data aggregated from four Department of Defense (DoD) studies with participant-level data (n=254) were grouped into pooled HBO2 and sham intervention groups. Changes from baseline to post-intervention on PCS, PTSD, and neuropsychological measures were assessed using linear mixed models to evaluate main intervention and intervention-by-baseline PTSD effects. Potential dose-response relationships to oxygen partial pressures were investigated. Intervention effects from three other published studies with summary-level participant data (n=135) were also summarized. Results: Pooled DoD data analyses indicated trends toward improvement favoring HBO2 for PCS (Rivermead Total Score: -2.3, 95% CI [-5.6, 1.0], p=0.18); PTSD (PTSD Checklist Total Score: -2.7, 95% CI [-5.8, 0.4], p=0.09); and significant improvement in verbal memory (CVLT-II Trial 1-5 Free Recall: 3.8; 95% CI [1.0, 6.7], p=0.01). A dose-response trend to increasing oxygen partial pressure was also found, with a greater HBO2 effect in mTBI-associated PTSD suggested. The direction of results was consistent with other published studies. Conclusions: A definitive clinical trial, with an appropriate control group, should be considered to identify the optimal HBO2 dosing regimen for individuals with mTBI-associated PTSD ± PCS.

Background Audiology clinics have many tools available to evaluate auditory and vestibular complaints. However, many tools lack established normative ranges across the life span. We conducted this study to establish reference ranges across the life span for audiology/vestibular measures commonly used to evaluate patients with traumatic brain injury. Materials and Methods In this repeated measures study, 75 adults, ages 18-65 years, without a history of traumatic brain injury, underwent robust auditory/vestibular evaluations three times over six months, including rotational chair, videonystagmography, computerized dynamic posturography, vestibular evoked myogenic potentials, and retinal fundoscopy. Results Age effect was notable for transient evoked otoacoustic emissions, pure-tone audiometry, auditory brainstem response, auditory middle latency response, and auditory-steady state response at 4000 hertz (Hz). Older participants (50-65 years) were more likely to have delayed latency horizontal saccades, positional nystagmus, slowed lower-extremity motor control responses, and delayed latency ocular vestibular evoked myogenic potentials. Low to mid-frequency horizontal (0.003-4 Hz) and mid-frequency vertical (1-3 Hz) vestibulo-ocular reflex, otolith-mediated reflexes, dynamic visual acuity and balance measures were generally not influenced by age. Females had larger static subjective visual testing offset angles, longer cervical vestibular evoked myogenic potential P1 latency, faster velocity horizontal saccades, and quicker motor control latency for large backward translations than age-matched males. Conclusion These reference ranges can be used to discern impairment within the auditory and vestibular pathway following traumatic brain injury in young to middle-aged adults. ID TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT01925963.

Introduction Global outcomes can strengthen inferences from clinical trials. We evaluate global outcomes for persistent post-concussive symptoms (PCS) after mild traumatic brain injury (mTBI) in two clinical trials of hyperbaric oxygen (HBO2) in United States service members. Methods During study design, outcomes of symptom, cognitive, and functional impairments planned for a trial of HBO2 for PCS (HOPPS) were weighted and grouped into different domains to formulate the composite outcome total score. The composite outcome was compared between the intervention groups in HOPPS and those in a subsequent HBO2 trial (BIMA) for validation. Additionally, two post hoc global outcome measures were explored, including one composed of components that demonstrated favorable characteristics in both studies and another via components used in another TBI randomized trial (COBRIT). Results In total, 143 active-duty or veteran military personnel were randomized across the two studies. Composite total scores improved from baseline for HBO2 (mean ± SD -2.9±9.0) and sham (-2.9±6.6) groups in HOPPS but did not differ significantly between groups (p=0.33). In BIMA, 13-week changes from baseline favored the HBO2 group (-3.6±6.4) versus sham (-0.3±5.2; p=0.02). No between-group differences were found when COBRIT composite scoring was applied to BIMA. Overall, HBO2 effects were maximized when the post hoc global measure derived from both studies was applied to the data. Conclusions Composite total scores in HOPPS and BIMA were consistent with primary study results. The global measures considered may offer utility as endpoints to achieve maximal HBO2 effect in future trials of the mTBI population. Ids clinicaltrials.gov Identifiers NCT01611194 (BIMA) and NCT01306968 (HOPPS).

Introduction: Individuals with persistent symptoms after mild traumatic brain injury (mTBI) often have auditory complaints. In this study, we used the auditory brainstem response (ABR) to determine whether cochlear synaptopathy could explain auditory symptoms. Methods: 69 adult military service members with mTBI and 25 adults without brain injury (NCT01611194 and NCT01925963) completed pure-tone audiometry, ABR, and central auditory processing tests. All participants were male, ages 21-50. Results: 37/69 mTBI participants had measurable hearing loss, while another 20-30% had hearing complaints or tinnitus. While mTBI participants with measurable hearing loss had reduced wave I and III amplitude and decreased III-V interpeak latency, those with no measurable hearing loss did not significantly differ from controls on any ABR parameter. Those with measurable hearing loss were also more likely to have abnormal central auditory processing. mTBI participants with no measurable hearing loss but who reported hearing concerns had some ABR findings (III-V interpeak latency, I and V amplitudes, V/I amplitude ratio) more like the measurable hearing loss mTBI group than normative controls. Conclusion: Cochlear synaptopathy may have contributed to some of the auditory impairment in service members with mTBI with measurable hearing loss. However, these results are likely confounded by cochlear hair cell damage.