Diagnosing mild traumatic brain injury using saliva RNA compared to cognitive and balance testing

Clinical and Translational Medicine

Samantha Johnson¹  Aaron Roberts¹  Chuck Monteith²  Thomas R. Campbell³  Miguel Madeira⁴  Callan D. McLoughlin⁵  Matthew Badia⁵  Zofia Gagnon⁵  Robert P. Olympia⁶  Jason Randall⁷  Matthew Heller⁸  Hallie Zwibel⁸  Cayce Onks⁹  Jayson Loeffert⁹  Frank Middleton^1,10  Raymond Y. Kim^1,11  Christopher Neville^1,12  Kevin J. Zhen^1,13  Steven D. Hicks^1,13  Andrea C. Loeffert^1,13  Rebekah Mannix^1,14  Samantha DeVita^1,15  Gregory Fedorchak^1,15  Aakanksha Rangnekar^1,15  John Leddy^1,16  Mohammad N. Haider^1,16  Michael N. Dretsch^1,17  Aaron M. Yengo‐Kahn^1,18  Justin Wenzel^1,18 

[1] Adena Bone and Joint Center Adena Regional Medical Center Chillicothe Ohio;Athletic Training Department Colgate University Hamilton New York;Athletic Training Department Old Dominion University Norfolk Virginia;Department of Biology, School of Science Marist College Poughkeepsie New York;Department of Biomedical Science Marist College Poughkeepsie New York;Department of Emergency Medicine Penn State College of Medicine Hershey Pennsylvania;Department of Environmental Science School of Science Marist College Poughkeepsie New York;Department of Family Medicine New York Institute of Technology College of Osteopathic Medicine Old Westbury New York;Department of Family Medicine Penn State College of Medicine Hershey Pennsylvania;Department of Neuroscience and Physiology SUNY Upstate Medical University Syracuse New York;Department of Orthopedics and Rehabilitation Penn State College of Medicine Hershey Pennsylvania;Department of PT Education, Orthopedics, and Neuroscience SUNY Upstate Medical University Syracuse New York;Department of Pediatrics Penn State College of Medicine Hershey Pennsylvania;Division of Emergency Medicine, Boston Children's Hospital Harvard Medical School Boston Massachusetts;Quadrant Biosciences Syracuse New York;UBMD Orthopedics and Sports Medicine, Jacobs School of Medicine and Biomedical Sciences State University of New York Buffalo New York;US Army Medical Research Directorate‐West Walter Reed Army Institute of Research Joint Base Lewis–McChord Washington;Vanderbilt Sports Concussion Center Vanderbilt University Medical Center Nashville Tennessee;

关键词: balance;    biomarker;    concussion;    diagnosis;    neurocognition;    RNA;   

DOI  :  10.1002/ctm2.197

来源: DOAJ

【 摘 要 】

Abstract Background Early, accurate diagnosis of mild traumatic brain injury (mTBI) can improve clinical outcomes for patients, but mTBI remains difficult to diagnose because of reliance on subjective symptom reports. An objective biomarker could increase diagnostic accuracy and improve clinical outcomes. The aim of this study was to assess the ability of salivary noncoding RNA (ncRNA) to serve as a diagnostic adjunct to current clinical tools. We hypothesized that saliva ncRNA levels would demonstrate comparable accuracy for identifying mTBI as measures of symptom burden, neurocognition, and balance. Methods This case‐control study involved 538 individuals. Participants included 251 individuals with mTBI, enrolled ≤14 days postinjury, from 11 clinical sites. Saliva samples (n = 679) were collected at five time points (≤3, 4‐7, 8‐14, 15‐30, and 31‐60 days post‐mTBI). Levels of ncRNAs (microRNAs, small nucleolar RNAs, and piwi‐interacting RNAs) were quantified within each sample using RNA sequencing. The first sample from each mTBI participant was compared to saliva samples from 287 controls. Samples were divided into testing (n = 430; mTBI = 201 and control = 239) and training sets (n = 108; mTBI = 50 and control = 58). The test set was used to identify ncRNA diagnostic candidates and create a diagnostic model. Model accuracy was assessed in the naïve test set. Results A model utilizing seven ncRNA ratios, along with participant age and chronic headache status, differentiated mTBI and control participants with a cross‐validated area under the curve (AUC) of .857 in the training set (95% CI, .816‐.903) and .823 in the naïve test set. In a subset of participants (n = 321; mTBI = 176 and control = 145) assessed for symptom burden (Post‐Concussion Symptom Scale), as well as neurocognition and balance (ClearEdge System), these clinical measures yielded cross‐validated AUC of .835 (95% CI, .782‐.880) and .853 (95% CI, .803‐.899), respectively. A model employing symptom burden and four neurocognitive measures identified mTBI participants with similar AUC (.888; CI, .845‐.925) as symptom burden and four ncRNAs (.932; 95% CI, .890‐.965). Conclusion Salivary ncRNA levels represent a noninvasive, biologic measure that can aid objective, accurate diagnosis of mTBI.

【 授权许可】

Unknown