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Biomarkers in Concussion

Matthew Eisenberg, Rebekah Mannix
PURPOSE OF REVIEW: Concussion is an increasingly common injury in children. We aim to review the basic epidemiology and management of acute concussion and highlight recent studies that have contributed to our understanding of care for this injury. RECENT FINDINGS: While concussion is considered a 'mild' form of traumatic brain injury, recent evidence suggests that as many as 30% of children are still symptomatic 1 month after injury. Although there is increasing interest in finding objective measures of injury and recovery, emerging imaging and serum biomarkers are not ready for routine clinical use...
March 13, 2018: Current Opinion in Pediatrics
Alex P Di Battista, Shawn G Rhind, Andrew J Baker, Rakesh Jetly, Jeff D Debad, Doug Richards, Michael G Hutchison
OBJECTIVES: To characterise a panel of neuroinjury-related blood biomarkers after sport-related concussion (SRC). We hypothesised significant differences in biomarker profiles between athletes with SRC and healthy controls at both subacute and medical clearance time points. METHODS: Thirty-eight interuniversity athletes were recruited over two athletic seasons (n = 19 SRC; n = 19 healthy matched-control). High-sensitivity immunoassay was used to evaluate 11 blood analytes at both the subacute phase after SRC and at medical clearance...
February 8, 2018: Brain Injury: [BI]
W Alan C Mutch, Michael J Ellis, Lawrence N Ryner, Patrick J McDonald, Marc P Morissette, Philip Pries, Marco Essig, David J Mikulis, James Duffin, Joseph A Fisher
Background: Preliminary studies suggest that sports-related concussion (SRC) is associated with alterations in cerebral blood flow (CBF) regulation. Here, we use advanced magnetic resonance imaging (MRI) techniques to measure CBF and cerebrovascular responsiveness (CVR) in individual SRC patients and healthy control subjects. Methods: 15 SRC patients (mean age = 16.3, range 14-20 years) and 27 healthy control subjects (mean age = 17.6, range 13-21 years) underwent anatomical MRI, pseudo-continuous arterial spin labeling (pCASL) MRI and model-based prospective end-tidal targeting (MPET) of CO2 during blood oxygenation level-dependent (BOLD) MRI...
2018: Frontiers in Neurology
Jaime Ramos-Cejudo, Thomas Wisniewski, Charles Marmar, Henrik Zetterberg, Kaj Blennow, Mony J de Leon, Silvia Fossati
Traumatic brain injury (TBI) and Alzheimer's disease (AD) are devastating neurological disorders, whose complex relationship is not completely understood. Cerebrovascular pathology, a key element in both conditions, could represent a mechanistic link between Aβ/tau deposition after TBI and the development of post concussive syndrome, dementia and chronic traumatic encephalopathy (CTE). In addition to debilitating acute effects, TBI-induced neurovascular injuries accelerate amyloid β (Aβ) production and perivascular accumulation, arterial stiffness, tau hyperphosphorylation and tau/Aβ-induced blood brain barrier damage, giving rise to a deleterious feed-forward loop...
January 30, 2018: EBioMedicine
Lia Maria Hocke, Chris C Duszynski, Chantel T Debert, Diane Dleikan, Jeffrey F Dunn
Concussion, or mild traumatic brain injury (mTBI), accounts for approximately 80% of all traumatic brain injuries across North America. The majority of mTBI patients recover within days to weeks, however, 14-36% of the time acute mTBI symptoms persist for months or even years and develop into persistent post-concussion symptoms (PPCS). There is a need to find biomarkers in patients with PPCS, to improve prognostic ability and to provide insight into the pathophysiology underlying chronic symptoms. Recent research has pointed towards impaired network integrity and cortical communication as a biomarker...
January 26, 2018: Journal of Neurotrauma
Kevin K Wang, Zhihui Yang, Tian Zhu, Yuan Shi, Richard Rubenstein, J Adrian Tyndall, Geoff T Manley
Traumatic brain injury (TBI) is a major worldwide neurological disorder of epidemic proportions. To date, there are still no FDA-approved therapies to treat any forms of TBI. Encouragingly, there are emerging data showing that biofluid-based TBI biomarker tests have the potential to diagnose the presence of TBI of different severities including concussion, and to predict outcome. Areas covered: The authors provide an update on the current knowledge of TBI biomarkers, including protein biomarkers for neuronal cell body injury (UCH-L1, NSE), astroglial injury (GFAP, S100B), neuronal cell death (αII-spectrin breakdown products), axonal injury (NF proteins), white matter injury (MBP), post-injury neurodegeneration (total Tau and phospho-Tau), post-injury autoimmune response (brain antigen-targeting autoantibodies), and other emerging non-protein biomarkers...
February 2018: Expert Review of Molecular Diagnostics
Robert E Becker, Nigel H Greig, Debomoy K Lahiri, Joseph Bledsoe, Sarah Majercik, Clive Ballard, Dag Aarsland, Lon S Schneider, Douglas Flanagan, Ramprakash Govindarajan, Mary Sano, Luigi Ferrucci, Dimitrios Kapogiannis
BACKGROUND: Concussion (mild) and other moderate traumatic brain injury (TBI) and Alzheimer's disease (AD) share overlapping neuropathologies, including neuronal pre-programmed cell death (PPCD), and clinical impairments and disabilities. Multiple clinical trials targeting mechanisms based on the Amyloid Hypothesis of AD have so far failed, indicating that it is prudent for new drug developments to also pursue mechanisms independent of the Amyloid Hypothesis. To address these issue, we have proposed the use of an animal model of concussion/TBI as a supplement to AD transgenic mice to provide an indication of an AD drug candidate's potential for preventing PPCD and resulting progression towards dementia in AD...
January 10, 2018: Current Alzheimer Research
Valentina Gallo, Damien McElvenny, Catherine Hobbs, Donna Davoren, Huw Morris, Sebastian Crutch, Henrik Zetterberg, Nick C Fox, Simon Kemp, Matthew Cross, Nigel K Arden, Madeleine A M Davies, Andrea Malaspina, Neil Pearce
INTRODUCTION: Relatively little is known about the long-term health of former elite rugby players, or former sportspeople more generally. As well as the potential benefits of being former elite sportspersons, there may be potential health risks from exposures occurring during an individual's playing career, as well as following retirement. Each contact sport has vastly different playing dynamics, therefore exposing its players to different types of potential traumas. Current evidence suggests that these are not necessarily comparable in terms of pathophysiology, and their potential long-term adverse effects might also differ...
December 26, 2017: BMJ Open
Robert E Becker, Dimitrios Kapogiannis, Nigel H Greig
INTRODUCTION: Neurodegenerative disorders have been a graveyard for hundreds of well-intentioned efforts at drug discovery and development. Concussion and other traumatic brain injuries (TBIs) and Alzheimer's disease (AD) share many overlapping pathologies and possible clinical links. METHODS: We searched the literature since 1995 using MEDLINE and Google Scholar for the terms concussion, AD, and shared neuropathologies. We also studied a TBI animal model as a supplement to transgenic (Tg) mouse AD models for evaluating AD drug efficacy by preventing neuronal losses...
December 12, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Foad Taghdiri, Jonathan Chung, Samantha Irwin, Namita Multani, Apameh Tarazi, Ahmed Ebraheem, Mozhgan Khodadadi, Ruma Goswami, Richard Wennberg, David Mikulis, Robin Ea Green, Karen Davis, Charles Tator, Moshe Eizenman, Maria Carmela Tartaglia
The aim of this study was to examine the potential utility of a self-paced saccadic eye movement as a marker of post-concussion syndrome (PCS) and monitoring the recovery from PCS. Fifty-nine persistently symptomatic participants with at least two concussions performed the self-paced saccade (SPS) task. We evaluated the relationships between the number of SPSs and (i) number of self-reported concussion symptoms, and (ii) integrity of major WM tracts (as measured by fractional anisotropy [FA], and mean diffusivity [MD]) that are directly or indirectly involved in saccadic eye movements and often affected by concussion...
December 14, 2017: Journal of Neurotrauma
Alexander Mark Weber, Carlos Torres, Alexander Rauscher
Myelin water imaging (MWI) provides mild traumatic brain injury (mTBI) researchers with a specific myelin biomarker and helps to further elucidate microstructural and microarchitectural changes of white matter after mTBI. Improvement of scanner hardware and software with the implementation of MWI across scanner platforms will likely result in increased research regarding the role of myelin in traumatic brain injury (TBI). Future research should include detailed investigation of myelin between 2 weeks and 2 months after injury, the use of MWI in moderate and severe TBI, and investigation of the role of myelin in chronic TBI...
February 2018: Neuroimaging Clinics of North America
Jeffrey P Guenette, Martha E Shenton, Inga K Koerte
Conventional neuroimaging examinations are typically normal in concussed young athletes. A current focus of research is the characterization of subtle abnormalities after concussion using advanced neuroimaging techniques. These techniques have the potential to identify biomarkers of concussion. In the future, such biomarkers will likely provide important clinical information regarding the appropriate time interval before return to play, as well as the risk for prolonged postconcussive symptoms and long-term cognitive impairment...
February 2018: Neuroimaging Clinics of North America
Scott A Bishop, Ryan T Dech, Przemyslaw Guzik, J Patrick Neary
Finding sensitive and specific markers for sports-related concussion is both challenging and clinically important. Such biomarkers might be helpful in the management of patients with concussion (i.e. diagnosis, monitoring and risk prediction). Among many parameters, blood flow-pressure metrics and heart rate variability (HRV) have been used to gauge concussion outcomes. Reports on the relation between HRV and both acute and prolonged concussion recovery are conflicting. While some authors report on differences in the low-frequency (LF) component of HRV during postural manipulations and postexercise conditions, others observe no significant differences in various HRV measures...
November 16, 2017: Clinical Physiology and Functional Imaging
Philip Sparks, Tim Lawrence, Stephan Hinze
OBJECTIVE: Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy associated with repeated subconcussive and concussive head injury. Clinical features include cognitive, behavioral, mood, and motor impairments. Definitive diagnosis is only possible at postmortem. Here, the utility of neuroimaging in the diagnosis of CTE is evaluated by systematically reviewing recent evidence for changes in neuroimaging biomarkers in suspected cases of CTE compared with controls. DATA SOURCES: Providing an update on a previous systematic review of articles published until December 2014, we searched for articles published between December 2014 and July 2016...
October 25, 2017: Clinical Journal of Sport Medicine: Official Journal of the Canadian Academy of Sport Medicine
Andrew S Nencka, Timothy B Meier, Yang Wang, L Tugan Muftuler, Yu-Chien Wu, Andrew J Saykin, Jaroslaw Harezlak, M Alison Brooks, Christopher C Giza, John Difiori, Kevin M Guskiewicz, Jason P Mihalik, Stephen M LaConte, Stefan M Duma, Steven Broglio, Thomas McAllister, Michael A McCrea, Kevin M Koch
The NCAA-DoD Concussion Assessment, Research, and Education (CARE) consortium is performing a large-scale, comprehensive study of sport related concussions in college student-athletes and military service academy cadets. The CARE "Advanced Research Core" (ARC), is focused on executing a cutting-edge investigative protocol on a subset of the overall CARE athlete population. Here, we present the details of the CARE ARC MRI acquisition and processing protocol along with preliminary analyzes of within-subject, between-site, and between-subject stability across a variety of MRI biomarkers...
October 24, 2017: Brain Imaging and Behavior
Brendan OʼConnell, Áine M Kelly, David Mockler, Matej Orešič, Karl Denvir, Garreth Farrell, Damir Janigro, Fiona Wilson
OBJECTIVES: To critically review current knowledge on the positive and negative predictive value of blood biomarkers for concussion; to illustrate the clinical and biological contexts that help evaluate the use of these markers in sport-related traumatic brain injuries (TBIs). METHODS: This systematic review was performed in accordance with PRISMA guidelines. We reviewed the measurement, clinical utility, endpoint, and biological significance of blood biomarkers in concussion...
October 12, 2017: Clinical Journal of Sport Medicine: Official Journal of the Canadian Academy of Sport Medicine
Breton M Asken, Molly J Sullan, Steven T DeKosky, Michael S Jaffee, Russell M Bauer
Importance: Scientific and lay interest in negative outcomes associated with exposure to repetitive brain trauma (RBT) continues to strengthen. Concerns about the association between RBT and dementia began more than a century ago, but have resurfaced in the last decade with the more recently described chronic traumatic encephalopathy (CTE). Chronic traumatic encephalopathy is a tauopathy associated with RBT that has become inextricably linked to conversations about sport-related concussion and mild traumatic brain injury...
October 1, 2017: JAMA Neurology
Sydney Candy, Irene Ma, Jill M McMahon, Michael Farrell, Richelle Mychasiuk
PRIMARY OBJECTIVE: Rugby is one of the few contact sports that do not mandate protective headgear, possibly because studies have shown poor efficacy for protection related to concussion pathology with existing headguards. RESEARCH DESIGN: Following innovative material technology utilization to produce headgear believed to have protective capabilities, this study examined the effects of a soft-shell headgear constructed from a novel viscoelastic material, on both behaviour and serum biomarkers after high and average impact force mild traumatic brain injuries (mTBI)...
2017: Brain Injury: [BI]
Eric Mercier, Pier-Alexandre Tardif, Peter Cameron, Brice Lionel Batomen Kuimi, Marcel Émond, Lynne Moore, Biswadev Mitra, Jérôme Frenette, Elaine de Guise, Marie-Christine Ouellet, Martine Bordeleau, Natalie Le Sage
This systematic review and meta-analysis aimed to determine the prognostic value of S-100β protein to identify patients with post-concussion symptoms following a mild traumatic brain injury (mTBI). A search strategy was submitted to seven databases from their inception to October 2016. Individual patient data were requested. Cohort studies evaluating the association between S-100β protein level and post-concussion symptoms assessed at least seven days after the mTBI were considered. Outcomes were dichotomised as persistent (>= 3 months) or early (>= 7 days < 3 months)...
October 2, 2017: Journal of Neurotrauma
Eric Mercier, Pier-Alexandre Tardif, Marcel Emond, Marie-Christine Ouellet, Élaine de Guise, Biswadev Mitra, Peter Cameron, Natalie Le Sage
OBJECTIVE: Mild traumatic brain injury (mTBI) has been insufficiently researched, and its definition remains elusive. Investigators are confronted by heterogeneity in patients, mechanism of injury and outcomes. Findings are thus often limited in generalisability and clinical application. Serum protein biomarkers are increasingly assessed to enhance prognostication of outcomes, but their translation into clinical practice has yet to be achieved. A systematic review was performed to describe the adult populations included and enrolled in studies that evaluated the prognostic value of protein biomarkers to predict postconcussion symptoms following an mTBI...
September 27, 2017: BMJ Open
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