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Symptom Resolution in Concussion Does Not Equal Brain Recovery

Damian McNamara
October 23, 2019

In one of the longest follow-up brain imaging studies in college athletes to date, investigators found specific adverse effects of concussion continue long after patients get medical clearance and return to play.

Although activity and communication between brain regions appeared normal in concussed athletes vs uninjured controls, concussion was associated with lower blood flow and changes in white matter tissue related to swelling on MRI, in findings that suggest recovery continued more than 1 year after traumatic brain injury (TBI).

"There is growing evidence that the effects of concussion may be long-lasting and that a history of concussion — particularly multiple concussions — is related to worse outcomes," lead investigator Nathan Churchill, PhD, research associate in the Neuroscience Research Program at St. Michael's Hospital in Toronto, told Medscape Medical News.

"However, we still know relatively little about how the brain recovers from concussion over the long-term, which is needed to understand the potential cause of these health concerns."

The study was published online October 16 in the journal Neurology.

Inaccurate Recovery Measure?

Medical societies recommend using symptom resolution to guide medical clearance decisions following concussion. However, Churchill and colleagues propose total brain recovery may lag behind clinical symptom resolution.

To learn more, investigators scanned the brains of 24 athletes with concussion 1 week after injury, at return to play (RTP), and 1 year after RTP. A large control cohort of 122 athletes also underwent MRI before the start of the season. Study participants came from a wide range of sports including volleyball, hockey, soccer, football, rugby, basketball, lacrosse, and water polo.

Participants had a mean age of 20 years and women accounted for approximately half of each cohort.

In addition to cerebral blood flow and mean diffusivity, the investigators assessed imaging results for global functional connectivity and fractional anisotropy.

Imaging included 3T MRI scans, resting-state functional MRI, arterial spin labeling, and diffusion tensor imaging. The researchers also considered time between concussion and symptom resolution, as well as severity of symptoms and a total symptom score using the Sport Concussion Assessment Tool 3.

Does the Brain Ever Return to Normal?

One year after return to play, MRI of the concussed athletes showed no significant effects on global functional connectivity or fractional anisotropy compared with controls.

However, MRI revealed differences in two other parameters, including significant reductions in cerebral blood flow among the concussed athletes (–10.03 mL/100 g/min; 95% confidence interval, –13.38 to –7.03) within middle frontal and temporal regions.

Similarly, the researchers found significant increases in mean diffusivity at 1 year post-clearance in this group (mean 1.32 × 10¯5 mm²/s; 95% CI, 0.86 - 1.78).

Correlations between these long-term effects of concussion and both the severity of symptoms and the length of time it took an athlete to RTP also emerged.

The study findings align with "growing evidence that neurobiological recovery may be incomplete at return to play," the researchers note. "The findings in this study indicate that more research is needed within the post-RTP time window to better understand optimal recovery time from a biological standpoint."

A lack of MRI scans prior to concussion is a potential limitation of the study. For this reason, the researchers were unable to assess if those with concussion returned to a normal pre-injury brain physiology.

"These findings suggest that brain recovery after concussion may be a more complex and longer-lasting process than we originally thought. This also raises questions about when — if ever — does the brain return to 'normal,' and whether the long-lasting brain changes we see are related to worse outcomes if the athletes sustain another concussion before recovery is completed," said Churchill.

Controversial Issue

Commenting on the findings for Medscape Medical News, Randolph W. Evans, MD, clinical professor of neurology at Baylor College of Medicine, Houston, Texas, and a member of Medscape Neurology's editorial advisory board, said whether there are any permanent effects of concussion is a long-standing and controversial topic.

He noted that Clarkson University history professor Stephen Casper, PhD, the author of a recent review article on the history of concussion, points out that "these are dangerous injuries with potentially life-changing consequences, ranging from permanent symptoms to degenerative neurological states."

Other researchers have indicated there are indirect, long-term effects of concussion, Evans noted. For example, prior studies show that people with normal brain function post-concussion experience cognitive impairment under stress from hypoxia induced by baric pressure changes.

"Churchill and colleagues provide additional structural and function MRI evidence that the brains of asymptomatic people with a history of concussion may not return to normal," said Evans.

Also commenting on study, David W. Kruse, MD, a sports medicine physician affiliated with Hoag Orthopedic Institute in Irvine, California, said it presents unique data about the impact of brain injury.

"This study contributes to the literature by presenting novel information regarding longitudinal changes in MRI parameters following a concussion event," Kruse, who was not involved with the current research, told Medscape Medical News. "There are still many gaps in our knowledge regarding the effects of concussion on brain physiology and the long-term consequences of those impacts."

"We are also still at the early stages of understanding what impact changes in MRI markers have on the clinical manifestations of concussion, both acute and long term," Kruse added. "This study provides an additional step toward a better understanding.

Churchill and Kruse report have disclosed no relevant financial relationships. Evans was an examiner as part of the NFL concussion settlement from May 2017 to June 2018 and evaluated 395 retired NFL players. Grants from the Canadian Institutes of Health Research, the Canadian Institute for Military and Veterans Health Research, and Siemens Healthineers Canada (which made the MRI equipment used in this study), supported the study.

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Reviewed on 10/25/2019
References
SOURCE: Medscape, October 23, 2019. Neurology. Published online October 16, 2019.

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