Systematic Review of Clinical Studies Examining Biomarkers of Brain Injury in Athletes after Sports-Related Concussion

Papa, Linda; Ramia, Michelle M.; Edwards, Damyan; Johnson, Brian D.; Slobounov, Semyon

doi:10.1089/neu.2014.3655

Cited by 125 publications

(110 citation statements)

References 71 publications

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“…Moreover, the power of biomarkers lies in early detection; thus, they should be detectable prior to histopathological changes and they should correlate with the severity of damage. 111 Interest in biomarkers for mTBI has increased dramatically over the past 2 decades following the increased understanding of CTE and the intensifying need for early diagnostics of brain injury. 41,111,112 However, the development of biomarkers specifically for CTE has proved elusive.…”

Section: Diagnostic Biomarkers Key Considerationsmentioning

confidence: 99%

“…111 Interest in biomarkers for mTBI has increased dramatically over the past 2 decades following the increased understanding of CTE and the intensifying need for early diagnostics of brain injury. 41,111,112 However, the development of biomarkers specifically for CTE has proved elusive. Numerous gaps remain in our understanding of the pathophysiological processes leading to the development of CTE.…”

Section: Diagnostic Biomarkers Key Considerationsmentioning

confidence: 99%

“…118 A recent systematic review examining biomarkers specifically for sports-related brain injury showed that 11 biomarkers have been investigated but none have been clinically validated. 111 This is partially due to the fact that the use of biomarkers for sports-related injuries and concussion is still a relatively new topic of interest; as a result, more research is needed for biomarker discovery.…”

Section: Biomarker Discovery: Current Prospects and Challengesmentioning

confidence: 99%

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Sports-related brain injuries: connecting pathology to diagnosis

Pan¹,

Connolly²,

Dangelmajer³

et al. 2016

FOC

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Neurosurg Focus 40 (4):E14, 2016M any sports-related brain injuries involve mild traumatic brain injuries (mTBIs), which result from physical blows to the head sustained over a period of time. Sports associated with an increased risk of head injury include American football, ice hockey, soccer, rugby, the martial arts, boxing, and bicycling. 21,90 These injuries are often unrecognized, undiagnosed, or underreported, which reflects the fact that this is a growing medical concern, often labeled a "silent epidemic." 8,66 Chronic exposure to mild brain injuries can result in long-term neurological consequences and represents a spectrum of disorders. The most remarkable outcome of mTBI is termed chronic traumatic encephalopathy (CTE), a clinical syndrome that is associated with neurodegeneration and behavioral, cognitive, and/or motor deficits. Although this disease has distinct pathological features, CTE is considered a diagnosis of exclusion because only postmortem biopsies can confirm the diagnosis. Therefore, new diagnostic methods need to be developed to: 1) inform patients of a definitive diagnosis, 2) better understand the epidemiology and risk factors of the disease, and 3) implement intervention programs to prevent any potential long-term complications. This review examines how understanding the pathology and molecular changes associated with repeated head trauma can lead to the discovery of novel imaging techniques and biomarkers. Mild Traumatic Brain Injury and CTEChronic traumatic encephalopathy has evolved from the so-called punch-drunk syndrome, which was used to describe a distinct neuropsychiatric condition that seemed to affect boxers, eventually becoming known as dementia pugilistica during the 1920s and 1930s. Symptoms such ABBrEvIATIoNs AD = Alzheimer's disease; APOE = apolipoprotein E; ASL = arterial spin labeling; BBB = blood-brain barrier; BOLD = blood oxygen level-dependent; CA = cornu ammonis; CTE = chronic traumatic encephalopathy; DTI = diffusion tensor imaging; FA = fractional anisotropy; fMRI = functional MRI; GFAP = glial fibrillary acidic protein; GRE = gradient recall echo; miRNA = microRNA; MRS = MR spectroscopy; mTBI = mild traumatic brain injury; NFL = National Football League; NFT = neurofibrillary tangle; NINDS = National Institute of Neurological Disorders and Stroke; NSE = neuron-specific enolase; p-tau = phosphorylated tau; SWI = susceptibility-weighted imaging; TDP-43 = TAR DNA-binding protein 43;18 F-FDDNP = 2-(1-{6- [(2-[fluorine-18] Brain injuries are becoming increasingly common in athletes and represent an important diagnostic challenge. Early detection and management of brain injuries in sports are of utmost importance in preventing chronic neurological and psychiatric decline. These types of injuries incurred during sports are referred to as mild traumatic brain injuries, which represent a heterogeneous spectrum of disease. The most dramatic manifestation of chronic mild traumatic brain injuries is termed chronic traumatic encephalopathy, which is associated with profo...

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Section: Diagnostic Biomarkers Key Considerationsmentioning

confidence: 99%

Section: Diagnostic Biomarkers Key Considerationsmentioning

confidence: 99%

Section: Biomarker Discovery: Current Prospects and Challengesmentioning

confidence: 99%

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Sports-related brain injuries: connecting pathology to diagnosis

Pan¹,

Connolly²,

Dangelmajer³

et al. 2016

FOC

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“…Historically, the analysis of exercise-induced stress relied on the measurement of functional outcome measures including strength, speed, power, and subjective scales to assess recovery status, the effectiveness of training programmes, and symptoms of overreaching. Recently, the use of biomarkers, which in a clinical setting are considered the gold standard [1][2][3][4][5][6], has become the quintessential monitoring tool in the field of sport and exercise medicine. This is primarily related to the ability of biomarkers to provide a quantitative individualistic snapshot of the homeostatic response of an individual at a certain time point.…”

Section: Introductionmentioning

confidence: 99%

Realising the Potential of Urine and Saliva as Diagnostic Tools in Sport and Exercise Medicine

Lindsay

Costello

2016

Sports Med

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Accurate monitoring of homeostatic perturbations following various psychophysiological stressors is essential in sports and exercise medicine. Various biomarkers are routinely used as monitoring tools in both clinical and elite sport settings. Blood collection and muscle biopsies, both invasive in nature, are considered the gold standard for the analysis of these biomarkers in exercise science. Exploring non-invasive methods of collecting and analysing biomarkers that are capable of providing accurate information regarding exercise-induced physiological and psychological stress is of obvious practical importance. This review describes the potential benefits, and the limitations, of using saliva and urine to ascertain biomarkers capable of identifying important stressors that are routinely encountered before, during, or after intense or unaccustomed exercise, competition, over-training, and inappropriate recovery. In particular, we focus on urinary and saliva biomarkers that have previously been used to monitor muscle damage, inflammation, cardiovascular stress, oxidative stress, hydration status, and brain distress. Evidence is provided from a range of empirical studies suggesting that urine and saliva are both capable of identifying various stressors. Although additional research regarding the efficacy of using urine and/or saliva to indicate the severity of exercise-induced psychophysiological stress is required, it is likely that these non-invasive biomarkers will represent "the future" in sports and exercise medicine.

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“…Innovative means such as prognostic blood markers have been investigated [5], and objective methods such as these have the potential to greatly facilitate assessment and management. The parallel here can be drawn with patients having chest pain; not all patients arriving with chest pain are assumed to have had an myocardial infarction, and years of research and investigation resulted in the use of troponin testing [6].…”

mentioning

confidence: 99%