Thursday, November 17, 2022

Hyperbaric oxygen therapy in children with post-concussion syndrome

Hadanny, A., Catalogna, M., Yaniv, S. et al. Hyperbaric oxygen therapy in children with post-concussion syndrome improves cognitive and behavioral function: a randomized controlled trial. Sci Rep 12, 15233 (2022).


Persistent post-concussion syndrome (PPCS) is a common and significant morbidity among children following traumatic brain injury (TBI) and the evidence for effective PPCS treatments remains limited. Recent studies have shown the beneficial effects of hyperbaric oxygen therapy (HBOT) in PPCS adult patients. This randomized, sham-control, double blind trial evaluated the effect of hyperbaric oxygen therapy (HBOT) on children (age 8–15) suffering from PPCS from mild-moderate TBI events six months to 10 years prior. Twenty-five children were randomized to receive 60 daily sessions of HBOT (n = 15) or sham (n = 10) treatments. Following HBOT, there was a significant increase in cognitive function including the general cognitive score (d = 0.598, p = 0.01), memory (d = 0.480, p = 0.02), executive function (d = 0.739, p = 0.003), PPCS symptoms including emotional score (p = 0.04, d = – 0.676), behavioral symptoms including hyperactivity (d = 0.244, p = 0.03), global executive composite score (d = 0.528, p = 0.001), planning/organizing score (d = 1.09, p = 0.007). Clinical outcomes correlated with significant improvements in brain MRI microstructural changes in the insula, supramarginal, lingual, inferior frontal and fusiform gyri. The study suggests that HBOT improves both cognitive and behavioral function, PPCS symptoms, and quality of life in pediatric PPCS patients at the chronic stage, even years after injury. Additional data is needed to optimize the protocol and to characterize the children who can benefit the most.

To date, very few randomized control trials in pediatric concussion patients have shown effective treatment, and many of those that have were focused on post-concussive headache—both acute and chronic—with limited efficacy, said Meeryo Choe, MD, FAAN, associate clinical professor and residency program director of the division of pediatric neurology at University of California, Los Angeles (UCLA), and associate director of the UCLA Steve Tisch BrainSPORT Program.

The current study adds to the existing literature on HBOT, “which has shown some improvement in physiologic markers in pre-clinical and clinical studies mostly in the more severe TBI, because it is the first to look at the use of hyperbaric oxygen therapy in a pediatric population with persistent symptoms after concussion,” she said.

“This study shows improvements in the subjects receiving the therapy in cognitive functioning, symptoms, and quality of life, and the authors suggest that this was associated with microstructural changes in specific areas utilizing diffusion tensor imaging,” Dr. Choe continued.

The sample size of 25,however, was very small, she said, noting that the investigators attributed this to resistance from parents who did not want to risk randomization to a sham therapy.

“This may be particularly true when their children may have been suffering with symptoms for years prior to participation in the study. In our experience, families whose kids have PPCS often seek out any treatment possible, including those without good evidence of efficacy. Some parents do ask us about HBOT, even though prior to this study there was only evidence in [adult] patients who had suffered a more severe TBI,” she added

“The current trial is ultimately underpowered to draw statistically solid conclusions as the authors acknowledge,” said Bethany Johnson-Kerner, MD, PhD, assistant professor of neurology and pediatrics program director of Brain Recovery Education in the division of child neurology at University of California, San Francisco Benioff Children's Hospital.

She also emphasized the low enrollment rate in the study and hesitation from parents, noting that this was “certainly a risk of prematurely publicizing the benefits of an intervention before there is sound evidence.”

Feasibility and safety were additional concerns in this trial because of the “intense protocol” of 60 daily sessions and the high side effect rate for participants—even if mild, Dr. Johnson-Kerner said. Importantly, the mechanism or mechanisms of this therapy are still unknown, she told Neurology Today. A 2017 Cochrane Review on this topic includes several previous studies for treating PPCS in adults, but the findings are inconsistent, she said.

Dr. Choe also pointed out that many of the participants in the current trial were years out from injury “with noted means of 11.6 years at inclusion and 6.7 years at injury.”

In the future, she suggested it would be interesting to see if this duration has an effect on the efficacy of HBOT depending on time since injury.

“Furthermore, preventing the development of PPCS with an intervention would be the ultimate goal for concussion therapy,” she added. “This heterogeneous patient population likely requires more individualized treatments based on symptoms as well as potential biomarkers that identify the specific endophenotype of concussion to guide the management.”

“PPCS is a very important pediatric medicine topic, and more research into sustainable treatments is needed,” Dr. Johnson-Kerner said, “including early recognition of patients at risk and connection to appropriate resources based on symptoms.”

It is important to identify those at risk for PPCS whether in primary care, trauma centers, or school settings, she said, and “to educate providers and educators that concussion symptoms, while generally transient, may last for longer than they think, and that children may need symptoms validated and assistance provided.”

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