REVIEW | doi:10.20944/preprints202307.0730.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: biomarkers; CTE; neurodegeneration; TBI; miRNA; exosomes; concussion; prodromal
Online: 12 July 2023 (11:35:53 CEST)
Chronic Traumatic Encephalopathy (CTE) is a neurodegenerative disease consistently associated with repetitive traumatic brain injuries (TBIs), which makes multiple professions, such as contact sports athletes, especially susceptible to its onset. There are currently no approved biomarkers to diagnose CTE, thus it can only be confirmed through a post-mortem brain autopsy. Several imaging and cerebrospinal fluid biomarkers have shown promise in the diagnosis. However, blood-based biomarkers can be more easily obtained and quantified, increasing their clinical feasibility and potential for prophylactic use. This article aimed to comprehensively review the studies into potential blood-based biomarkers of CTE, discussing common themes and limitations as well as suggesting future research directions. While the interest in blood-based biomarkers of CTE has recently increased, the research is still in its early stages. The main issue for many proposed biomarkers is their lack of selectivity for CTE. However, several molecules, such as tau phosphorylated on different epitopes, were able to discern CTE from different neurodegenerative diseases. Further, results from studies of exosomal biomarkers suggest that exosomes are a promising source of biomarkers reflective of the internal environment of the brain. Nonetheless, more longitudinal studies combining imaging, neurobehavioral and biochemical approaches are warranted to establish robust biomarkers of CTE.
COMMUNICATION | doi:10.20944/preprints202305.1998.v1
Subject: Public Health And Healthcare, Physical Therapy, Sports Therapy And Rehabilitation Keywords: Oculomotor pursuits; Eye-movement; Concussion; Assessment; Learning effect
Online: 29 May 2023 (08:40:42 CEST)
Mild traumatic brain injury (mTBI) is the most common brain injury, seen in sports, falls, vehicle, or workplace injuries. Concussion is the most common type of mTBI. Assessment of impairments from concussion are evolving, with oculomotor testing suggested as a key component in a multi-modality diagnostic protocol. The aim of this study was to evaluate the reliability of one eye-tracking system, the EyeGuide Focus. Seventy-five healthy adolescent and adult participants (adolescents: n=28; female=11, male=17, mean age 16.5 ± 1.4 years; adults n=47; female=22; male=25, mean age 26.7 ± 7.0 years) completed three repetitions of the EyeGuide Focus within the one session. Intraclass correlation coefficient (ICC) analysis showed the EyeGuide Focus had overall good reliability (ICC 0.79, 95%CI: 0.70, 0.86). However, a familiarization effect showing improvements in subsequent trials was noticeable in both cohorts (p<0.001) with adolescent participants showing greater familiarisation effects than adults. No differences were observed between sexes (p=0.69). Overall, the EyeGuide Focus was found to be reliable, but the observation of familiarization effects suggests that a standardized protocol of a minimum of three trials be employed, similar to other eye-movement testing applications.
REVIEW | doi:10.20944/preprints202311.1552.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: mild traumatic brain injury; post-concussion syndrome; exosomes; salivary biomarkers
Online: 24 November 2023 (11:27:49 CET)
Background: Alongside their long-term effects - post-concussion syndrome (PCS) - mild traumatic brain injuries (mTBI) are significant public health concerns. Currently, there is a lack of reliable biomarkers for diagnosing and monitoring mTBI and PCS. Exosomes are small extracellular vesicles secreted by cells that have recently emerged as a potential source of biomarkers for mTBI and PCS due to their ability to cross the blood-brain barrier and reflect the pathophysiology of brain injury. This study aimed to investigate the role of salivary exosomal biomarkers in mTBI and PCS. Methods: A systematic review using the PRISMA guidelines was conducted, and studies were selected based on their relevance to the topic. Results: Studies have shown that exosomal tau, phosphorylated tau (p-tau), amyloid beta (Aβ), and microRNAs (miRNAs) are potential biomarkers for mTBI and PCS. Specifically, elevated levels of exosomal tau and p-tau have been associated with mTBI and PCS, as well as with repetitive mTBI. Dysregulated exosomal miRNAs have also been observed in individuals with mTBI and PCS. Additionally, exosomal Prion cellular protein (PRPc), coagulation factor XIII (XIIIa), synaptogyrin-3, IL-6, and aquaporins have been identified as promising biomarkers for mTBI and PCS. Conclusion: Salivary exosomal biomarkers have the potential to serve as non-invasive and easily accessible diagnostic and prognostic tools for mTBI and PCS. Further studies are needed to validate these biomarkers and to develop standardized protocols for their use in clinical settings. Salivary exosomal biomarkers can improve the diagnosis, monitoring, and treatment of mTBI and PCS, leading to improved patient outcomes.
ARTICLE | doi:10.20944/preprints202310.0944.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Neuropsychological tests; youth football; concussion; cognition; helmets; head acceleration events
Online: 16 October 2023 (08:40:00 CEST)
Weight and age interact to modify cognitive effects of head acceleration events after two seasons of youth football Abstract This is a follow-up study of youth American football players in a second season of play. Season-one findings identified a relationship between a head acceleration measure (HITsp) and cognitive score changes with weight modifying the effect in 9 to 10 year-olds. Sixty-eight youth completed a second season of play wearing helmet-mounted sensors and were assessed with neuropsychological tests pre- and post-season. Regression analysis of the full sample demonstrated a small but significant negative effect of HAE on cognition as indexed by test score changes: R2 = .06, F = 4.06, p = .024. Outcome differences between those who started playing at ages nine to 10, compared to those who started between 11 and 13 were identified: t(66) = -3.39, p<.01, d = -.84, 95th CI -2.77 to -.72. Regression models including players’ weights found that the relationship of weight to outcome was different by group: greater negative cognitive effects were found in younger-heavier players (R2 = 0.21, F =3.21, p = 0.03) and older-lighter players (R2 = 0.18, F =4.26, p <.001). These findings confirmed a negative relationship of HAE and cognitive change and point to player weight as an important developmental factor to consider in understanding concussion biomechanics.
REVIEW | doi:10.20944/preprints202103.0449.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: vision rehabilitation; review of systems; traumatic brain injury; concussion; patient advocacy.
Online: 17 March 2021 (16:05:12 CET)
Treating a patient with traumatic brain injury requires an interdisciplinary approach because of the pervasive, profound and protean manifestations of this condition. In this review, key aspects of the medical history and review of systems will be described in order to highlight how the role of any provider must evolve to become a better patient advocate. Although this review is written from the vantage point of a vision care provider, it is hoped that patients, caregivers and providers will recognize the need for the team approach; it truly takes a village.
ARTICLE | doi:10.20944/preprints202007.0629.v1
Subject: Engineering, Automotive Engineering Keywords: smart textiles; pressure sensor; concussion detection; Velostat; football helmet; head impacts
Online: 26 July 2020 (02:34:43 CEST)
A Mild traumatic brain injury (mTBI) or concussion has become a public health problem in the United State. Sports and recreational activities are major sources of concussions; with the most incidents connected to American football. Recently, many companies and research institutions have started studying concussions and introduced some means of protection and some alarming systems of strong jolts. The major detection and protection system currently available on the market is the electronic helmet (e-helmet) composed of measurement devices to record head impact acceleration. The most commonly used devices in e-helmets are accelerometers to measure linear acceleration and gyroscopes for rotational/angular acceleration. Using smart textiles for concussion detection is currently uncommon and limited due to the lack of literature studying their voltage related errors. Actually, there are few works that characterize some voltage-force related errors for such type of sensors but for small impact forces and under bench testing while the behavior of those sensors was not described for higher ranges of applied forces and in field situations. This paper previews some common techniques used in e-helmets for concussion detection and highlights electronic textiles and smart fabric sensors that could be very useful for these applications. It discusses and validates the general behavior of such type of sensors under high impact forces and on field testing instead of bench testing, and also it characterizes the effect of increasing the thickness of the sensing element layer on the sensor. A custom-made pressure sensor was created of some available fabrics to be embedded within the padding of a football helmet to quantify the impacting force to the head. The sensor is mainly composed a Semi Conductive Polymer Composite SCPC layer with modifiable thickness that was modified three times with 0.2, 0.4, and 1.6mm to characterize the general behavior of the sensor due to a high amount of impacts and correlated with the thickness. A pendulum system was built to test the pressure sensors, while a special camera and an open-source video analysis software, Tracker was used to track the pendulum bob. The speed and the acceleration of the pendulum bob were measured, then the impact force was calculated and a voltage-force response was obtained. The results showed that no meaningful improvement occurs by small increase in the thickness but better sensor behavior could be obtained by significant increment to observe any difference. Despite that at a very high impacts, the suggested sensor with Velostat layers is not giving the real voltage readings that reflect the actual applied forces but it gives a helpful information that illustrate the distribution of the force through identification the place of the highest and lowest voltage readings regardless of the exact values of those readings. However, the proposed smart textile pressure sensor could be applicable in future e-helmet designs with additional research-based improvements especially on the structure of the sensing element layer to be able to withstand such high impacts which in turns improves the overall sensor performance and accurately measures pressure in concussion-inducing ranges.
REVIEW | doi:10.20944/preprints202306.0644.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: mild traumatic brain injury; post-concussion syndrome; neuroinflammation; pro-inflammatory cytokines; diagnosis; outcomes; recovery.
Online: 8 June 2023 (11:36:44 CEST)
Mild TBI (mTBI) accounts for most TBI cases, the leading cause of morbidity and mortality worldwide. Despite their high incidence, mTBI pathophysiology remains largely unknown. Recent studies have shown that the inflammatory response is activated early after mTBI and can persist for several weeks or months. However, limited evidence on the utility of inflammatory biomarkers as predictors of clinical outcomes in mTBI was previously provided. Thus, this study aims to provide an overview of the current knowledge on the role of inflammation in the pathogenesis of mTBI and the potential of some inflammatory biomolecules as biomarkers of mTBI. Thus, it was shown that the increase of IL-6, TNF-α, and IL-1β plasma levels could be implicated in the development of the early post-concussion symptoms. On the other hand, the persistence of the increased plasmatic concentrations of IL-10 and IL-8 for as long as six months following the brain injury event could suggest chronic inflammation leading to neuroinflammation and late or persistent symptoms. In this context, our findings showed that the inflammatory biomarkers could be relevant in diagnosing or predicting recovery or long-term outcomes of mTBI.
ARTICLE | doi:10.20944/preprints202001.0374.v1
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: mild traumatic brain injury; mTBI; concussion; cognitive; sensorimotor; visual; postural balance; methylation; 5-mC%; blood
Online: 31 January 2020 (04:28:21 CET)
People who suffer a mild traumatic brain injury (mTBI) have heterogeneous symptoms and disease trajectories, which make it difficult to precisely diagnose and assess complications long-term. Insufficient information is available regarding how to precisely diagnose and assess mTBI. This study identified and compared deficits in cognitive, psychosocial, visual functions, and balance performance between college students with and without histories of mTBI. Global DNA methylation ratio (5-mC%) in blood was also compared as a peripheral epigenetic marker. Twenty-five volunteers participated in this pilot study, including 11 mTBI cases (27.3% females; mean age of 28.7 years, SD=5.92) and 14 healthy controls (64.3% females; mean age of 22.0, SD=4.13). All the participants were assessed for cognitive (by NIH toolbox—executive function, memory, and processing speed), psychological (by PROMIS—depression, anxiety, and sleep disturbances), visual function (by King-Devick and binocular accommodative tests), postural balance performance (by a force plate), and blood 5-mC% (global methylation) levels. Students with mTBI reported significantly poorer episodic memory, severe anxiety, and more sleep disturbance problems. They also had higher blood 5-mC% level (all p’s<.05). No significant differences were found in visual function and postural balance. These findings validate changes in cognitive, psychosocial, and global DNA methylation long after mTBI.
ARTICLE | doi:10.20944/preprints202112.0264.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: concussion; mild traumatic brain injury; working memory; long-term cognitive outcome; support vector machine classifier; personalized prediction
Online: 16 December 2021 (10:24:08 CET)
Concussion, also known as mild traumatic brain injury (mTBI), commonly causes transient neurocognitive symptoms, but in some cases, it causes cognitive impairment, including working memory (WM) deficit, which can be long-lasting and impede a patient’s return to work. The predictors of long-term cognitive outcomes following mTBI remain unclear because abnormality is often absent in structural imaging findings. The purpose of the study was to determine whether machine learning-based models using functional magnetic resonance imaging (fMRI) biomarkers and demographic or neuropsychological measures at baseline could effectively predict 1-year cognitive outcomes of concussion. We conducted a prospective, observational study of patients with mTBI who were compared with demographically-matched healthy controls enrolled between September 2015 to August 2020. Baseline assessments were collected within the first week of injury, and follow-ups were conducted at 6 weeks, 3 months, 6 months, and 1 year. Potential demographic, neuropsychological, and fMRI features were selected according to the significance of correlation with the estimated changes in WM ability. The support vector machine classifier was trained using these potential features and estimated changes in WM between the predefined time periods. Patients demonstrated significant cognitive recovery at the third month, followed by worsened performance after 6 months, which persisted until 1 year after concussion. Approximately half of the patients experienced prolonged cognitive impairment at 1-year follow up. Satisfactory predictions were achieved for patients whose WM function did not recover at 3 months (accuracy=87.5%), 6 months (accuracy=83.3%), 1 year (accuracy=83.3%), and performed worse at 1-year follow-up compared to baseline assessment (accuracy=83.3%). This study demonstrated the feasibility of personalized prediction for long-term postconcussive WM outcomes based on baseline fMRI and demographic features, opening a new avenue for early rehabilitation intervention in selected individuals with possible poor long-term cognitive outcomes.
REVIEW | doi:10.20944/preprints202012.0314.v1
Subject: Social Sciences, Psychology Keywords: Very mild Traumatic Brain Injury; Animal models (rodents); Post-concussion syndrome; neuro-behavioral changes; “inflammaging”; brain apoptosis
Online: 14 December 2020 (09:33:51 CET)
Post-concussion syndrome, recently recognized as a complication of mild traumatic brain injury, is considered a consequence of the summative effect of multiple concussions received over lifetime. In elderlies, the main mild brain trauma mechanism is fall (low impact force). Many falls are often not reported or noticed but may generate serious medical and medico-legal consequences. Our research question was to find if a single, very mild brain trauma can induce neuro-behavioral consequences in elderlies. One database was queried (PubMed – MeSH terminology) looking for histopathological, neuro-cognitive and behavioral changes that can be generated by sub-concussional trauma in senescent rodents, in comparison with young animals. 41 published research articles were selected. 17 of them used very mild brain trauma in young and senescent animals, in the same experiment (6 rats and 11 mice). 24 articles evaluated the effect of sub-threshold brain trauma in adult animals (no control group). Five trauma models were used (blast models were excluded). Neuro-inflammatory changes were detected immediate after very mild primary impact. In young animals, observed pathology disappeared fast (after 3 to 7 days). Increased apoptosis, mild axonal injury in white matter tracts plus maladaptive astrogliosis and microglial activation was stronger in aged animals, persisted over time (8 months) and significantly altered animals’ cognition and behavior. Associated preexisting pathology (hypertension, tau protein deposits, microbleeds, reactive inflammation) was often responsible for amplification of the primary impact results. As translation of observation is the weak spot of pathology and behavior animal research, further investigation is needed before to conclude that even a single, very mild brain trauma may have medical consequences on human senescent brain.