Sports-related brain injuries: connecting pathology to diagnosis

Abstract

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...

Acute White-Matter Abnormalities in Sports-Related Concussion: A Diffusion Tensor Imaging Study from the NCAA-DoD CARE Consortium

“…Because an initial pathophysiological response after concussion is believed to involve diffuse axonal injury in the brain white matter, [8][9][10][11][12][13][14][15] diffusion tensor imaging (DTI), an MRI technique focusing on white matter, 16,17 is recommended [18][19][20][21] and has been found to have adequate diagnostic sensitivity to changes in brain structure after SRC. 22 Specifically, DTI produces two summary metrics, fractional anisotropy (FA) and mean diffusivity (MD), and two orthogonal metrics, axial diffusivity (AD) and radial diffusivity (RD).…”

Endoplasmic Reticulum Stress Modulation as a Target for Ameliorating Effects of Blast Induced Traumatic Brain Injury

“…One of the most significant and characteristic pathologic changes is the accumulation of tau neurofibrillary tangles at the glia limitans and perivascular spaces. 5 Puvenna and colleagues recently showed that glymphatic clearance of tau is impaired following repetitive traumatic brain injury in CTE specimens. 6 We expanded upon these findings showing that TBI can contribute to tauopathy leading to CTE, Alzheimer's disease (AD), or, in rare cases, CTE/ AD.…”

Apolipoprotein E epsilon 4 (APOE‐ε4) genotype is associated with decreased 6‐month verbal memory performance after mild traumatic brain injury

“…However, an Indian cohort of mild-to-moderate TBI patients at 6 months showed no clear differences in neuropsychological test performance by APOE-ε4 status (Pruthi et al, 2010). Reports of association between ε4 carriers and postconcussional symptoms months to years postinjury also exist (Sundström et al, 2007;Merritt & Arnett, 2016;Pan et al, 2016).…”