Microrna Biomarkers on Day of Injury Among Patients with Post Concussive Symptoms at 28-Days: A Prospective Cohort Study
  • * (Excluding Mailing and Handling)

Abstract

Background: After mild traumatic brain injury (mTBI), some patients experience symptoms that persist for weeks to months. Recovery from mTBI is primarily assessed using selfreported symptom questionnaires. Blood biomarkers, including microRNA species, have shown promise to assist diagnosis of mTBI, however, little is known about how blood microRNA measures might predict symptom recovery.

Objective: The aim of this study was to investigate the variances in plasma microRNAs on the day of injury between individuals with mTBI who report post-concussive symptoms at the 28- day mark and those who do not.

Methods: Patients who presented to an adult, tertiary referral hospital emergency department on the day of the injury and were diagnosed with isolated mTBI (n=35) were followed up for 28 days. Venous blood samples were collected and symptom severity was assessed using the Rivermead Post-Concussion Symptom Questionnaire (RPQ) on the day of injury and at 28 days. Patients who reported ongoing symptoms of total RPQ score ≥10 or at least one symptom severity ≥2, were compared to those with lesser symptom severity or symptom resolution.

Results: There were 9 (25.7%; 95%CI: 12.5-43.3) patients who reported persistent symptoms. Day of injury plasma miR-223-3p levels were significantly higher in individuals with ongoing symptoms compared to those without, however, no such differences were observed for miRs 142- 3p, 423-3p, 32-5p, 144-3p, and let-7f-5p.

Conclusion: Acute plasma miR-223-3p levels appear to detect patients who later have persistent symptoms after mTBI. The results demonstrate the potential utility for such biomarkers to assist in decisions towards early referral for therapy after mTBI.

[1]
Lefevre-Dognin C, Cogné M, Perdrieau V, Granger A, Heslot C, Azouvi P. Definition and epidemiology of mild traumatic brain injury. Neurochirurgie 2021; 67(3): 218-21.
[http://dx.doi.org/10.1016/j.neuchi.2020.02.002] [PMID: 32387427]
[2]
Broglio SP, McAllister T, Katz BP, et al. The natural history of sport-related concussion in collegiate athletes: Findings from the NCAA-DoD CARE consortium. Sports Med 2022; 52(2): 403-15.
[http://dx.doi.org/10.1007/s40279-021-01541-7] [PMID: 34427877]
[3]
Henry LC, Elbin RJ, Collins MW, Marchetti G, Kontos AP. Examining recovery trajectories after sport-related concussion with a multimodal clinical assessment approach. Neurosurgery 2016; 78(2): 232-41.
[http://dx.doi.org/10.1227/NEU.0000000000001041] [PMID: 26445375]
[4]
Makdissi M, Schneider KJ, Feddermann-Demont N, et al. Approach to investigation and treatment of persistent symptoms following sport-related concussion: A systematic review. Br J Sports Med 2017; 51(12): 958-68.
[http://dx.doi.org/10.1136/bjsports-2016-097470] [PMID: 28483928]
[5]
Carroll EL, Outtrim JG, Forsyth F, et al. Mild traumatic brain injury recovery: A growth curve modelling analysis over 2 years. J Neurol 2020; 267(11): 3223-34.
[http://dx.doi.org/10.1007/s00415-020-09979-x] [PMID: 32535683]
[6]
Nelson LD, Temkin NR, Dikmen S, et al. Recovery after mild traumatic brain injury in patients presenting to US level I trauma centers. JAMA Neurol 2019; 76(9): 1049-59.
[http://dx.doi.org/10.1001/jamaneurol.2019.1313] [PMID: 31157856]
[7]
Langer LK, Alavinia SM, Lawrence DW, et al. Prediction of risk of prolonged post-concussion symptoms: Derivation and validation of the TRICORDRR (Toronto Rehabilitation Institute Concussion Outcome Determination and Rehab Recommendations) score. PLoS Med 2021; 18(7): e1003652.
[http://dx.doi.org/10.1371/journal.pmed.1003652] [PMID: 34237056]
[8]
Atif H, Hicks SD. A review of MicroRNA biomarkers in traumatic brain injury. J Exp Neurosci 2019; 13.
[http://dx.doi.org/10.1177/1179069519832286] [PMID: 30886525]
[9]
Mitra B, Reyes J, O’Brien WT, et al. Micro-RNA levels and symptom profile after mild traumatic brain injury: A longitudinal cohort study. J Clin Neurosci 2022; 95: 81-7.
[http://dx.doi.org/10.1016/j.jocn.2021.11.021] [PMID: 34929656]
[10]
Carroll L, Cassidy JD, Holm L, Kraus J, Coronado V. Methodological issues and research recommendations for mild traumatic brain injury: The who collaborating centre task force on mild traumatic brain injury. J Rehabil Med 2004; 36(0): 113-25.
[http://dx.doi.org/10.1080/16501960410023877] [PMID: 15083875]
[11]
Tator CH, Davis HS, Dufort PA, et al. Postconcussion syndrome: Demographics and predictors in 221 patients. J Neurosurg 2016; 125(5): 1206-16.
[http://dx.doi.org/10.3171/2015.6.JNS15664] [PMID: 26918481]
[12]
Bean J. Rey auditory verbal learning test. In: Kreutzer JS, DeLuca J, Caplan B, Eds. Encyclopedia of Clinical Neuropsychology. New York, NY: Springer New York 2011; pp. 2174-5.
[http://dx.doi.org/10.1007/978-0-387-79948-3_1153]
[13]
Maruff P, Thomas E, Cysique L, et al. Validity of the CogState brief battery: Relationship to standardized tests and sensitivity to cognitive impairment in mild traumatic brain injury, schizophrenia, and AIDS dementia complex. Arch Clin Neuropsychol 2009; 24(2): 165-78.
[http://dx.doi.org/10.1093/arclin/acp010] [PMID: 19395350]
[14]
Oride MKH, Marutani JK, Rouse MW. DeLAND PN. Reliability study of the pierce and king-devick saccade tests. Optom Vis Sci 1986; 63(6): 419-24.
[http://dx.doi.org/10.1097/00006324-198606000-00005] [PMID: 3728637]
[15]
Lovibond SH, Lovibond PF. Manual for the depression anxiety stress scales. Sydney: Psychology Foundation of Australia 1995.
[16]
Mitra B, Rau TF, Surendran N, et al. Plasma micro-RNA biomarkers for diagnosis and prognosis after traumatic brain injury: A pilot study. J Clin Neurosci 2017; 38: 37-42.
[http://dx.doi.org/10.1016/j.jocn.2016.12.009] [PMID: 28117263]
[17]
McDonald SJ, O’Brien WT, Symons GF, et al. Prolonged elevation of serum neurofilament light after concussion in male Australian football players. Biomark Res 2021; 9(1): 4.
[http://dx.doi.org/10.1186/s40364-020-00256-7] [PMID: 33422120]
[18]
McMahon PJ, Hricik A, Yue JK, et al. Symptomatology and functional outcome in mild traumatic brain injury: Results from the prospective TRACK-TBI study. J Neurotrauma 2014; 31(1): 26-33.
[http://dx.doi.org/10.1089/neu.2013.2984] [PMID: 23952719]
[19]
Zhu Z, Huang X, Du M, et al. Recent advances in the role of miRNAs in post-traumatic stress disorder and traumatic brain injury. Mol Psychiatry 2023; 28(7): 2630-44.
[http://dx.doi.org/10.1038/s41380-023-02126-8] [PMID: 37340171]
[20]
Sharma S, Eghbali M. Influence of sex differences on microRNA gene regulation in disease. Biol Sex Differ 2014; 5(1): 3.
[http://dx.doi.org/10.1186/2042-6410-5-3] [PMID: 24484532]
[21]
Pinchi E, Luigi C, Paola S, et al. MicroRNAs: The new challenge for traumatic brain injury diagnosis. Curr Neuropharmacol 2020; 18(4): 319-31.
[http://dx.doi.org/10.2174/1570159X17666191113100808] [PMID: 31729300]
[22]
Mitra B, Major BP, Reyes J, et al. MicroRNA biomarkers for diagnosis of mild traumatic brain injury and prediction of persistent symptoms: A prospective cohort study. J Clin Neurosci 2023; 115: 38-42.
[http://dx.doi.org/10.1016/j.jocn.2023.07.011] [PMID: 37480731]