Hyperbaric oxygen for post-concussive symptoms in United States military service members: a randomized clinical trial.

BACKGROUND: In prior military randomized trials, participants with persistent symptoms after mild traumatic brain injury (TBI) reported improvement regardless of receiving hyperbaric oxygen (HBO2) or sham intervention. This study's objectives were to identify outcomes for future efficacy trials and describe changes by intervention. METHODS: This Phase II, randomized, double-blind, sham-controlled trial enrolled military personnel with mild TBI and persistent post-concussive symptoms. Participants were randomized to receive 40 HBO2 (1.5 atmospheres absolute (ATA), ⟩99% oxygen, 60 minutes) or sham chamber sessions (1.2 ATA, room air, 60 minutes) over 12 weeks. Participants and evaluators were blinded to allocation. Outcomes assessed at baseline, 13 weeks and six months included symptoms, quality of life, neuropsychological, neurological, electroencephalography, sleep, auditory, vestibular, autonomic, visual, neuroimaging, and laboratory testing. Participants completed 12-month questionnaires. Intention-to-treat results are reported. RESULTS: From 9/11/2012 to 5/19/2014, 71 randomized participants received HBO2 (n=36) or sham (n=35). At baseline, 35 participants (49%) met post-traumatic stress disorder (PTSD) criteria. By the Neurobehavioral Symptom Inventory, the HBO2 group had improved 13-week scores (mean change -3.6 points, P=0.03) compared to sham (+3.9 points). In participants with PTSD, change with HBO2 was more pronounced (-8.6 vs. +4.8 points with sham, P=0.02). PTSD symptoms also improved in the HBO2 group, and more so in the subgroup with PTSD. Improvements regressed at six and 12 months. Hyperbaric oxygen improved some cognitive processing speed and sleep measures. Participants with PTSD receiving HBO2 had improved functional balance and reduced vestibular complaints at 13 weeks. CONCLUSIONS: By 13 weeks, HBO2 improved post-concussive and PTSD symptoms, cognitive processing speed, sleep quality, and balance function, most dramatically in those with PTSD. Changes did not persist beyond six months. Several outcomes appeared sensitive to change; additional studies are warranted.

Comprehensive Evaluation of Healthy Volunteers Using Multi-Modality Brain Injury Assessments: An Exploratory, Observational Study.

Introduction: Even though mild traumatic brain injury is common and can result in persistent symptoms, traditional measurement tools can be insensitive in detecting functional deficits after injury. Some newer assessments do not have well-established norms, and little is known about how these measures perform over time or how cross-domain assessments correlate with one another. We conducted an exploratory study to measure the distribution, stability, and correlation of results from assessments used in mild traumatic brain injury in healthy, community-dwelling adults. Materials and Methods: In this prospective cohort study, healthy adult men and women without a history of brain injury underwent a comprehensive brain injury evaluation that included self-report questionnaires and neurological, electroencephalography, sleep, audiology/vestibular, autonomic, visual, neuroimaging, and laboratory testing. Most testing was performed at 3 intervals over 6 months. Results: The study enrolled 83 participants, and 75 were included in the primary analysis. Mean age was 38 years, 58 were male, and 53 were civilians. Participants did not endorse symptoms of post-concussive syndrome, PTSD, or depression. Abnormal neurological examination findings were rare, and 6 had generalized slowing on electroencephalography. Actigraphy and sleep diary showed good sleep maintenance efficiency, but 21 reported poor sleep quality. Heart rate variability was most stable over time in the sleep segment. Dynavision performance was normal, but 41 participants had abnormal ocular torsion. On eye tracking, circular, horizontal ramp, and reading tasks were more likely to be abnormal than other tasks. Most participants had normal hearing, videonystagmography, and rotational chair testing, but computerized dynamic posturography was abnormal in up to 21% of participants. Twenty-two participants had greater than expected white matter changes for age by MRI. Most abnormal findings were dispersed across the population, though a few participants had clusters of abnormalities. Conclusions: Despite our efforts to enroll normal, healthy volunteers, abnormalities on some measures were surprisingly common. Trial Registration: This study was registered at www.clinicaltrials.gov, trial identifier NCT01925963.

Linear analysis of heart rate variability in post-concussive syndrome.

Heart rate variability (HRV) represents measurable output of coordinated structural and functional systems within the body and brain. Both mild traumatic brain injury (mTBI) and HRV are modulated by changes in autonomic nervous system function. We present baseline HRV results from an ongoing mTBI clinical trial. HRV was assessed via 24-hour ambulatory electrocardiography; recordings were segmented by physiological state (sleep, wakefulness, exercise, standing still). Time, frequency, and spatial domain measures were summarized and compared with symptoms, sleep quality, and neurological examination. Median low frequency/high frequency (LF/HF) ratio exceeded 1.0 across segments, indicating prevalence of sympathetic modulation. Abnormal Sharpened Romberg Test was associated with 29% LF/HF decrease (95% CI [2.1, 47.7], p=0.04); pathological nystagmus associated with decreased standard deviation of electrocardiogram R-R interval (SDNN) index (25% decrease, 95% CI [0.8, 43.4], p=0.04). Increased sympathetic modulation was associated with increased anger scores (19% LF/HF increase with 5-point State Trait Anger Expression Inventory-2 trait anger increase (95% CI [1.2, 39.1], p=0.04)). A 13% HF increase (95% CI [2.1, 25.7], p=0.02) was observed with increased Pittsburgh Sleep Quality Index scores. These results support autonomic nervous system dysfunction in service members after mTBI. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01611194; https://clinicaltrials.gov/show/NCT01611194.