The multimodal, electroencephalogram (EEG)-based Concussion Index is a reliable tool for aiding diagnosis of concussion at time of injury and may be useful in determining when athletes can return to the field following mild traumatic brain injury, researchers found.
When it comes to concussions, there is no objective standard for making a diagnosis — instead, physicians base diagnosis on the patient’s subjective report of signs and symptoms. That process may delay definitive diagnosis, which can lead to slower recovery and impairments in academic, cognitive, and social functioning, Jeffrey J. Bazarian, MD, of the Department of Emergency Medicine at the University of Rochester in Rochester, New York, and colleagues explained in JAMA Network Open.
The Concussion Index, a multimodal tool that incorporates neurocognitive performance and vestibular symptoms with qEEG data to enhance classification accuracy, “accurately discriminated between athlete controls without concussion and athletes with concussion with a sensitivity of 84.9%, specificity of 76.0%, and area under the curve of 0.89,” according to results from a derivation study.
Bazarian and colleagues conducted their analysis to validate the Concussion Index’s performance for classification accuracy and prediction of concussion at the time of injury in an independent cohort of athletes with concussion.
“This validation study confirmed that a multimodal, EEG-based Concussion Index can be used with high accuracy to distinguish between athletes with a concussion and those without on the day of injury, supporting the use of the Concussion Index as an objective indicator of brain function impairment at the time of injury for participants with concussion,” Bazarian and colleagues wrote. “Significant differences between the Concussion Index at the time of injury and the Concussion Index at [return to play] RTP may be associated with changes over time in the population with concussion when they are clinically cleared to RTP. Likewise, the demonstration of stability of the Concussion Index across time among the controls allows for confidence in the interpretation of changes when seen in the population with concussion, suggesting the potential utility for monitoring change throughout the recovery period and as a component of the clinical assessment of readiness to RTP.”
And, they added, the easy-to-use Concussion Index “lends itself to being incorporated into existing standard assessments of concussion to aid in clinical diagnosis and assessment of readiness to RTP.” Data from this study was used in support of the FDA clearance of the Concussion Index as a biomarker in a hand-held, multimodal, multiparameter assessment device for patients with mild traumatic brain injury (BrainScope).
For their prospective diagnostic cohort study, Bazarian and colleagues assembled a cohort of 580 athletes ages 13-25 years — 207 with concussion (124 [59.9%] male; mean [SD] age, 19.4 [2.5] years) and 373 matched controls without concussion (187 [50.1%] male; mean [SD] age, 19.6 [2.2] years). Study participants were evaluated at 10 clinical sites between Feb. 4, 2017, and March 20, 2019. Patients were “assessed with electroencephalography, cognitive testing, and symptom inventories within 72 hours of injury [day 0], at return to play [RTP], and 45 days after return to play [RTP+45],” they explained. “Variables from the multimodal assessment were used to generate a Concussion Index at each time point. Athletes with concussion had experienced a witnessed head impact, were removed from play for five days or more, and had an initial Glasgow Coma Scale score of 13 to 15 [total range, 3-15, where 3 indicates severe injury and 15 indicates no or minor injury].”
Athlete controls (Glasgow Coma Scale score of 15 at day 0) were matched to participants with concussion for age, sex, and type of sport played. Participants with known neurological disease or history of traumatic brain injury within the last year were excluded.
The study’s main outcome was classification accuracy of the Concussion Index at time of injury using a prespecified cutoff of 70 or less — Concussion Index scores ranged from 0-100, where ≤70 indicated the patient likely had a concussion and >70 indicated it was unlikely the patient had a concussion.
“The Concussion Index had a sensitivity of 86.0% (95% CI, 80.5%-90.4%), specificity of 70.8% (95% CI, 65.9%-75.4%), negative predictive value of 90.1% (95% CI, 86.1%-93.3%), positive predictive value of 62.0% (95% CI, 56.1%-67.7%), and area under receiver operator characteristic curve of 0.89,” the study authors found. “At day 0, the mean (SD) Concussion Index among athletes with concussion was significantly lower than among athletes without concussion (75.0 [14.0] vs 32.7 [27.2]; P< .001). Among athletes with concussion, there was a significant increase in the Concussion Index between day 0 and return to play, with a mean (SD) paired difference between these time points of −41.2 (27.0) (P< .001).”
By comparison, differences in Concussion Index between day 0 and RTP+45 for athletes without concussion were near 0, “demonstrating the stability of the Concussion Index over time among athletes without concussion,” they found. And, at RTP, “the Concussion Index of 78.2% (95% CI, 71.8%-83.7%) of the athletes with concussion was at or above the predetermined threshold for control athletes. This implies that a high percentage of athletes with concussion cleared to RTP by standard clinical practice (using the graded RTP protocol) had Concussion Indexes in the range of 90% of control athletes without concussion, consistent with recovery.”
Bazarian and colleagues pointed out that, while 78.2% of athletes who had concussion improved to within the range of uninjured controls by RTP, this result suggests that some athletes with concussion may have been cleared for RTP before brain function impairment was resolved — a finding that supports previous literature “attesting to the persistence of brain function abnormalities in individuals with sports-related concussion beyond the point when clinical symptoms have resolved,” they wrote. “Because current RTP graded protocols have a significant dependence on participant-reported symptoms, which may resolve when brain function impairment persists, the potential importance of an additional objective measure as part of the final assessment of RTP is highlighted.”
Bazarian and colleagues acknowledged the lack of intermediate time points for assessment of change throughout recovery and the use of a restricted age range (13-25 years) as study limitation.
This validation study confirmed that a multimodal, EEG-based Concussion Index can be used with high accuracy to distinguish between athletes with and without concussion on the day of injury.
Significant differences between the Concussion Index at the time of injury versus at return to play [RTP], and the stability of the Concussion Index across time among controls without concussion, suggest the tool’s potential utility for monitoring change throughout the recovery period and as a component of the clinical assessment of readiness to RTP.
John McKenna, Associate Editor, BreakingMED™
The study was funded in part by contract W911QY-14-C-0098 to BrainScope Co Inc from the U.S. Navy (Naval Health Research Center).
All authors were principal investigators at one of the clinical data acquisition sites participating in the research, whose institutions received contracts to support participant recruitment, consenting, and data acquisition and have no competing financial interests to disclaim.
Bazarian and coauthors Casa, Lopez, Schnyer, Yeargin, and Covassin reported receiving grants from BrainScope Co. Inc. during the conduct of the study. Bazarian reported receiving personal fees from Abbott and Q30 Innovations outside the submitted work. Coauthor Elbin reported receiving grants and consulting fees from BrainScope Co. Inc. during the conduct of the study. Coauthor Neville reported being an equity owner of Quadrant Biosciences Inc. outside the submitted work. No other disclosures were reported.
Cat ID: 130
Topic ID: 82,130,254,728,791,730,130,474,138,192,925