Hyperbaric Oxygen Therapy for the Management of Mild and Moderate Traumatic Brain Injury: A Single-Center Experience.

BACKGROUND: Hyperbaric oxygen therapy (HBOT) has been shown to be an effective modality in the management of a variety of conditions. However, its role in the treatment of traumatic brain injury (TBI) remains an area of controversy. This study aims to evaluate the safety and outcomes of HBOT in managing the long-term sequelae of TBI. METHODS: The records of TBI patients who underwent increments of 40 sessions of HBOT at 1.5 atmosphere absolute at a single medical center were reviewed. The outcome measures included physical, cognitive (i.e., Trail Making Test, parts A and B; U.S. Department of Veterans Affairs' Evaluation of Cognitive Impairment and Subjective Symptoms tool), and single-photon emission computed tomography findings. The complications and withdrawals were recorded. RESULTS: During the study period, 17 patients underwent HBOT to manage the long-term sequelae of their TBI. Of the 17 patients, 12 (70.6%) completed 120 HBOT sessions and were evaluated 3 months after treatment. All 12 patients had statistically significant improvements in their Trail Making Test, parts A and B, and U.S. Department of Veterans Affairs' Evaluation of Cognitive Impairment and Subjective Symptoms scores (P < 0.05). Additionally, single-photon emission computed tomography depicted increased cerebral blood flow and oxygen metabolism among studied subjects compared with the baseline values. A total of 5 patients withdrew from the study, which was related to new-onset headaches associated with HBOT for 1 patient. CONCLUSIONS: HBOT using 1.5 atmosphere absolute in increments of 40 sessions was found to be a safe and effective modality in the management of the long-term sequelae of TBI. HBOT should be considered in the management of this patient population.

Treatment of Persistent Postconcussion Syndrome With Repetitive Transcranial Magnetic Stimulation Using Functional Near-Infrared Spectroscopy as a Biomarker of Response: Protocol for a Randomized Controlled Clinical Trial.

BACKGROUND: Approximately one-third of all concussions lead to persistent postconcussion syndrome (PPCS). Repetitive transcranial magnetic stimulation (rTMS) is a form of noninvasive brain stimulation that has been extensively used to treat refractory major depressive disorder and has a strong potential to be used as a treatment for patients with PPCS. Functional near-infrared spectroscopy (fNIRS) has already been used as a tool to assess patients with PPCS and may provide insight into the pathophysiology of rTMS treatment in patients with PPCS. OBJECTIVE: The primary objective of this research is to determine whether rTMS treatment improves symptom burden in patients with PPCS compared to sham treatment using the Rivermead postconcussion symptom questionnaire. The secondary objective is to explore the neuropathophysiological changes that occur following rTMS in participants with PPCS using fNIRS. Exploratory objectives include determining whether rTMS treatment in participants with PPCS will also improve quality of life, anxiety, depressive symptoms, cognition, posttraumatic stress, and function secondary to headaches. METHODS: A total of 44 adults (18-65 years old) with PPCS (>3 months to 5 years) will participate in a double-blind, sham-controlled, concealed allocation, randomized clinical trial. The participants will engage in either a 4-week rTMS treatment protocol or sham rTMS protocol (20 treatments). The left dorsolateral prefrontal cortex will be located through Montreal Neurologic Institute coordinates. The intensity of the rTMS treatment over the left dorsolateral prefrontal cortex will be 120% of resting motor threshold, with a frequency of 10 Hz, 10 trains of 60 pulses per train (total of 600 pulses), and intertrain interval of 45 seconds. Prior to starting the rTMS treatment, participant and injury characteristics, questionnaires (symptom burden, quality of life, depression, anxiety, cognition, and headache), and fNIRS assessment will be collected. Repeat questionnaires and fNIRS will occur immediately after rTMS treatment and at 1 month and 3 months post rTMS. Outcome parameters will be analyzed by a 2-way (treatment × time) mixed analysis of variance. RESULTS: As of May 6, 2021, 5 participants have been recruited for the study, and 3 have completed the rTMS protocol. The estimated completion date of the trial is May 2022. CONCLUSIONS: This trial will expand our knowledge of how rTMS can be used as a treatment option of PPCS and will explore the neuropathophysiological response of rTMS through fNIRS analysis. TRIAL REGISTRATION: ClinicalTrials.gov NCT04568369; https://clinicaltrials.gov/ct2/show/NCT04568369. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/31308.

Hyperbaric oxygen therapy for mild traumatic brain injury persistent postconcussion syndrome: a randomized controlled trial.

Persistent postconcussion syndrome (PPCS) after mild traumatic brain injury (mTBI) is a significant public health and military problem for which there is limited treatment evidence. The aim of this study was to determine whether forty 150 kPa hyperbaric oxygen therapies (HBOTs) can improve symptoms and cognitive function in subjects with the PPCS of mTBI, using a randomized controlled crossover design with 2-month follow-up. Sixty-three civilian and military subjects with mTBI/PPCS were randomized to either 40 HBOTs at 150 kPa/60 minutes, once daily, 5 days per week in 8 weeks or an equivalent no-treatment control period. The Control Group was then crossed over to HBOT. Subjects underwent symptom, neuropsychological, and psychological testing, before and after treatment or control with retesting 2 months after the 40th HBOT. Fifty subjects completed the protocol with primary outcome testing. HBOT subjects experienced significant improvements in Neurobehavioral Symptom Inventory, Memory Index, Automated Neuropsychological Assessment Metrics, Hamilton Depression Scale, Hamilton Anxiety Scale, Post-Traumatic Stress Disorder Checklist, Pittsburgh Sleep Quality Index, and Quality Of Life after Brain Injury compared to the Control Group. After crossing over to HBOT the Control Group experienced near-identical significant improvements. Further improvements were experienced by both groups during the 2-month follow-up period. These data indicate that 40 HBOTs at 150 kPa/60 minutes demonstrated statistically significant improvements in postconcussion and Post-Traumatic Stress Disorder symptoms, memory, cognitive functions, depression, anxiety, sleep, and quality of life in civilian and military subjects with mTBI/PPCS compared to controls. Improvements persisted at least 2 months after the 40th HBOT. The study was registered on ClinicalTrials.gov (NCT02089594) on March 18, 2014 and with the U.S. Food and Drug Administration under Investigational New Drug #113823. The Institutional Review Boards of the United States Army Medical Research and Materiel Command Office of Research Protections Human Research Protection Office and the Louisiana State University School of Medicine (approval No. 7381) approved the study on May 13, 2014 and December 20, 2013, respectively.

Postconcussion syndrome.

Postconcussion syndrome (PCS) is a heterogeneous condition comprised of a set of signs and symptoms in somatic, cognitive, and emotional domains. PCS is a controversial concept because of differing consensus criteria, variability in presentation, and lack of specificity to concussion. Whereas symptoms of concussion resolve in most individuals over days to weeks, a minority of individuals experience symptoms persisting months to years. The clinical consequences of concussion may be best conceptualized as two multidimensional disorders: (1) a constellation of acute symptoms termed early-phase posttraumatic disorder (commonly headache, dizziness, imbalance, fatigue, sleep disruption, impaired cognition, photo- and phonophobia); and (2) late-phase posttraumatic disorder, consisting of somatic, emotional, and cognitive symptoms. This phase is highly influenced by various psychosocial factors and is much less specific to the brain injury itself. Risk factors for development of a late-phase disorder include a high early symptom burden (e.g., headache, fatigue), a history of multiple concussions, psychiatric conditions (anxiety, depression), longer duration of unconsciousness or amnesia, and younger age. Successful treatment requires thoughtful differential diagnosis, including consideration of comorbid and premorbid conditions and other possible contributing factors. Treatment should include a hierarchic, sequential approach to management of treatable symptoms that impact functioning, such as depression, anxiety, insomnia, headache, musculoskeletal pain, and vertigo. A guided prescription of aerobic exercise is beneficial for early- and late-phase disorders after concussion.