Journal article

Chronic traumatic encephalopathy neuropathology might not be inexorably progressive or unique to repetitive neurotrauma

Grant L Iverson, Andrew J Gardner, Sandy R Shultz, Gary S Solomon, Paul McCrory, Ross Zafonte, George Perry, Lili-Naz Hazrati, C Dirk Keene, Rudolph J Castellani

BRAIN | OXFORD UNIV PRESS | Published : 2019

Abstract

In the 20th century, chronic traumatic encephalopathy (CTE) was conceptualized as a neurological disorder affecting some active and retired boxers who had tremendous exposure to neurotrauma. In recent years, the two research groups in the USA who have led the field have asserted definitively that CTE is a delayed-onset and progressive neurodegenerative disease, with symptoms appearing in midlife or decades after exposure. Between 2005 and 2012 autopsy cases of former boxers and American football players described neuropathology attributed to CTE that was broad and diverse. This pathology, resulting from multiple causes, was aggregated and referred to, in toto, as the pathology 'characteristi..

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Funding Acknowledgements

G.L.I. has been reimbursed by the government, professional scientific bodies, and commercial organizations for discussing or presenting research relating to MTBI and sport-related concussion at meetings, scientific conferences, and symposiums. He has a clinical practice in forensic neuropsychology involving individuals who have sustained mild TBIs (including athletes). He has received honorariums for serving on research panels that provide scientific peer review of programs. He is a co-investigator, collaborator, or consultant on grants relating to mild TBI funded by the federal government and other organizations. He has received research support from test publishing companies in the past, including ImPACT (R) Applications Systems, Psychological Assessment Resources, and CNS Vital Signs. He has received grant funding from the National Football League and salary support from the Harvard Integrated Program to Protect and Improve the Health of NFLPA Members. He serves as a scientific advisor for BioDirection, Inc, SWAY Operations, LLC, and Highmark, Inc. He acknowledges unrestricted philanthropic support from the Mooney-Reed Charitable Foundation, Heinz Family Foundation, and ImPACT (R) Applications, Inc. A.J.G. has a clinical practice in neuropsychology involving individuals who have sustained sportrelated concussion (including current and former athletes). He has been a contracted concussion consultant to the Rugby Australia since July 2016. He has received travel funding from the Australian Football League (AFL) to present at the Concussion in Football Conference in 2013 and 2017. Previous grant funding includes the NSW Sporting Injuries Committee, the Brain Foundation (Australia), and the Hunter Medical Research Institute (HMRI), supported by Jennie Thomas, and the HMR, supported by Anne Greaves. He is currently funded through an NHMRC Early Career Fellowship, and Hunter New England Local Health District, Research, Innovation and Partnerships Health Research & Translation Centre and Clinical Research Fellowship Scheme, and the University of Newcastle's Priority Research Centre for Stroke and Brain Injury. S.R.S. is funded through an NHMRC Career Development Fellowship and an NHMRC Project Grant. He has also received research funding from the Australian Football League (AFL) to investigate the neurological effects of participating in amateur Australian rules football. He is an employee of Monash University and Alfred Health. G.S.S. has received honoraria and expense reimbursements from government, professional and scientific organizations for presenting research relating to sportrelated concussion at meetings, scientific conferences, and symposiums. He is a full-time employee of the Vanderbilt University Medical Center, where he has a clinical practice in sports neuropsychology involving patients who have sustained concussions. He is the consulting neuropsychologist for the Nashville Predators, Tennessee Titans, and the athletic departments of the University of Tennessee, Tennessee Tech University, and Vanderbilt University, fees paid to institution. He is the Senior Medical Advisor for the National Football League Department of Health and Safety. P.M. is a co-investigator on competitive grants relating to mild TBI funded by several governmental and other organizations. He is funded under a Fellowship awarded by the National Health and Medical Research Council of Australia and is employed at the Florey Institute of Neuroscience and Mental Health. He has a clinical consulting practice in neurology, including medico-legal work.He has been reimbursed by the government, professional scientific bodies, and commercial organizations for discussing or presenting research relating to MTBI and sport-related concussion at meetings, scientific conferences, and symposiums. He has not directly received any research funding, or monies other than travel reimbursements from the AFL, FIFA or the NFL and does not hold any individual shares in or receive monies from any company related to concussion or brain injury assessment or technology. He acknowledges unrestricted philanthropic support from CogState Inc. (2001-16). He is the chair of the scientific committees of the International Concussion and Head Injury Research Foundation in London and the Sports Surgery Clinic in Dublin. P.M. did not receive any form of financial support directly related to this manuscript. R.Z. has been partially supported by NIDILRR, NIH, and USARMC: NIDILRR: 90DP07039-03-00, 90SI5007-02-04,90 D P0060; USAMRC-W81XWH-112-0210, NIH: 4 U01NS086090-04; 5R24HD082302-02;5U01NS091951-03. He also serves as co-principal investigator on a T-32 and receives funding from the Football Players Health Study at Harvard University, which is funded by the NFL Players Association. R.Z. received royalties from (i) Oakstone for an educational CD-Physical Medicine and Rehabilitation a Comprehensive Review; and (ii) Demos publishing for serving as co-editor of the text Brain Injury Medicine. R.Z. serves on the Scientific Advisory Board of Myomo, Oxeia Biopharma, ElMINDA, and BioDirection. He also evaluates patients in the MGH Brain and Body-TRUST Program which is funded by the NFL Players Association. G.P. acknowledges funding from the Alzheimer's Association, Semmes Foundation, NIH (G12-MD007591), and Lowe Foundation. He is on the board and owns equity in Neurotrope and Neurotez, he is an advisor and owns equity in Investicure, and he has research support and is an advisor for Phoenix Biotech. C.D.K. has received honoraria and expense reimbursements from government, professional, and scientific organizations for presenting research relating to sport-related concussion and traumatic brain injury at meetings, scientific conferences, and symposiums. He is supported in part through the Nancy and Buster Alvord Chair in Neuropathology, intramural support unrelated to this study, and NIH (U01 AG006781, P50 AG05136, P30 AG049638, R01 ES02618, R01 AG057915, R21 AG046883, U01 AG006781), DOD (W81XWH-17-1-0330), and foundation (Henry Jackson Foundation and Allen Institute for Brain Science) grants. R.J.C. has been reimbursed for travel for speaking at educational programs and has received fees for medicolegal consulting. He has received intramural research funding at Western Michigan University School of Medicine, unrelated to this study. He is subcontracted to the NIH Neurobiobank at the University of Maryland and the Lieber Institute for Brain Development. L-N.H. acknowledges research funding from the Canadian Institutes of Health Research and the National Institute of Neurological Disorders and Stroke. She has served as a consultant and expert witness in the area of neurotrauma and neuropathology.