Douglas I Katz1, Charles Bernick1, David W Dodick1, Jesse Mez1, Megan L Mariani1, Charles H Adler1, Michael L Alosco1, Laura J Balcer1, Sarah J Banks1, William B Barr1, David L Brody1, Robert C Cantu1, Kristen Dams-O'Connor1, Yonas E Geda1, Barry D Jordan1, Thomas W McAllister1, Elaine R Peskind1, Ronald C Petersen1, Jennifer V Wethe1, Ross D Zafonte1, Éimear M Foley1, Debra J Babcock1, Walter J Koroshetz1, Yorghos Tripodis1, Ann C McKee1, Martha E Shenton1, Jeffrey L Cummings1, Eric M Reiman1, Robert A Stern2. 1. From the Boston University CTE Center (D.I.K.), Department of Neurology, Boston University School of Medicine, Boston; Brain Injury Program (D.I.K.), Encompass Health Braintree Rehabilitation Hospital, Braintree, MA; University of Washington Memory & Brain Wellness Clinic (C.B.), Department of Neurology, University of Washington School of Medicine, Seattle; Department of Neurology (D.W.D., C.H.A.), Mayo Clinic, Scottsdale, AZ; Boston University CTE Center (J.M., M.L.A.), Boston University Alzheimer's Disease Center, Department of Neurology, Boston University School of Medicine; Boston University CTE Center (M.L.M.), Boston University School of Medicine, MA; Departments of Neurology (L.J.B.), Ophthalmology, and Population Health, New York University Grossman School of Medicine; Departments of Neurosciences and Psychiatry University of California San Diego (S.J.B.), La Jolla; Departments of Neurology and Psychiatry (W.B.B.), New York University Grossman School of Medicine; Center for Neuroscience and Regenerative Medicine (D.L.B.), Uniformed Services University of the Health Sciences, Department of Neurology, F. Edward Hebert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD; Boston University CTE Center (R.C.C.), Boston University Alzheimer's Disease Center, Departments of Neurology and Neurosurgery, Boston University School of Medicine, MA; Departments of Rehabilitation Medicine and Neurology (K.D.-O.C.), Icahn School of Medicine, Mount Sinai, New York; Department of Neurology (Y.E.G.), Barrow Neurological Institute, Phoenix, AZ; Rancho Los Amigos National Rehabilitation Center (B.D.J.), Downey, CA; Department of Neurology (B.D.J.), Keck School of Medicine of USC. Los Angeles, CA; Departments of Psychiatry and Neurology (T.W.M.), Indiana University School of Medicine, Indianapolis; Veterans Affairs Northwest Mental Illness (E.R.P.), Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, WA; Department of Psychiatry and Behavioral Sciences (E.R.P.), University of Washington School of Medicine, Seattle; Mayo Clinic Alzheimer's Disease Research Center (R.C.P.), Mayo Clinic, Rochester, MN; Department of Psychiatry and Psychology (J.V.W.), Mayo Clinic, Scottsdale, AZ; Department of Physical Medicine and Rehabilitation (R.D.Z.), Spaulding Rehabilitation Hospital, Massachusetts General Hospital, Brigham and Women's Hospital, Harvard Medical School, Boston; Faculty of Psychology and Neuroscience (É.M.F.), Maastricht University, the Netherlands, Department of Psychiatry, University of Cambridge, United Kingdom; National Institute of Neurological Disorders and Stroke (D.J.B.), National Institutes of Health; National Institute of Neurological Disorders and Stroke (W.J.K.), Bethesda, MD; Boston University CTE Center (Y.T.), Boston University Alzheimer's Disease Center, Boston University School of Medicine, Department of Biostatistics, Boston University School of Public Health; Boston University CTE Center (A.C.M.), Boston University Alzheimer's Disease Center, Departments of Neurology and Pathology & Laboratory Medicine, Boston University School of Medicine; VA Boston Healthcare System (A.C.M.), US Department of Veteran Affairs, MA; Psychiatry Neuroimaging Laboratory (M.E.S.), Departments of Psychiatry and Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Chambers-Grundy Center for Transformative Neuroscience (J.L.C.), Department of Brain Health, University of Nevada School of Integrated Health Sciences; Cleveland Clinic Lou Ruvo Center for Brain Health (J.L.C.), Las Vegas, NV; Banner Alzheimer's Institute (E.M.R.), Arizona State University; Department of Psychiatry (E.M.R.), University of Arizona, Phoenix, AZ; and Boston University CTE Center (R.A.S.), Boston University Alzheimer's Disease Center, Departments of Neurology, Neurosurgery, and Anatomy & Neurobiology, Boston University School of Medicine, MA. 2. From the Boston University CTE Center (D.I.K.), Department of Neurology, Boston University School of Medicine, Boston; Brain Injury Program (D.I.K.), Encompass Health Braintree Rehabilitation Hospital, Braintree, MA; University of Washington Memory & Brain Wellness Clinic (C.B.), Department of Neurology, University of Washington School of Medicine, Seattle; Department of Neurology (D.W.D., C.H.A.), Mayo Clinic, Scottsdale, AZ; Boston University CTE Center (J.M., M.L.A.), Boston University Alzheimer's Disease Center, Department of Neurology, Boston University School of Medicine; Boston University CTE Center (M.L.M.), Boston University School of Medicine, MA; Departments of Neurology (L.J.B.), Ophthalmology, and Population Health, New York University Grossman School of Medicine; Departments of Neurosciences and Psychiatry University of California San Diego (S.J.B.), La Jolla; Departments of Neurology and Psychiatry (W.B.B.), New York University Grossman School of Medicine; Center for Neuroscience and Regenerative Medicine (D.L.B.), Uniformed Services University of the Health Sciences, Department of Neurology, F. Edward Hebert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD; Boston University CTE Center (R.C.C.), Boston University Alzheimer's Disease Center, Departments of Neurology and Neurosurgery, Boston University School of Medicine, MA; Departments of Rehabilitation Medicine and Neurology (K.D.-O.C.), Icahn School of Medicine, Mount Sinai, New York; Department of Neurology (Y.E.G.), Barrow Neurological Institute, Phoenix, AZ; Rancho Los Amigos National Rehabilitation Center (B.D.J.), Downey, CA; Department of Neurology (B.D.J.), Keck School of Medicine of USC. Los Angeles, CA; Departments of Psychiatry and Neurology (T.W.M.), Indiana University School of Medicine, Indianapolis; Veterans Affairs Northwest Mental Illness (E.R.P.), Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, WA; Department of Psychiatry and Behavioral Sciences (E.R.P.), University of Washington School of Medicine, Seattle; Mayo Clinic Alzheimer's Disease Research Center (R.C.P.), Mayo Clinic, Rochester, MN; Department of Psychiatry and Psychology (J.V.W.), Mayo Clinic, Scottsdale, AZ; Department of Physical Medicine and Rehabilitation (R.D.Z.), Spaulding Rehabilitation Hospital, Massachusetts General Hospital, Brigham and Women's Hospital, Harvard Medical School, Boston; Faculty of Psychology and Neuroscience (É.M.F.), Maastricht University, the Netherlands, Department of Psychiatry, University of Cambridge, United Kingdom; National Institute of Neurological Disorders and Stroke (D.J.B.), National Institutes of Health; National Institute of Neurological Disorders and Stroke (W.J.K.), Bethesda, MD; Boston University CTE Center (Y.T.), Boston University Alzheimer's Disease Center, Boston University School of Medicine, Department of Biostatistics, Boston University School of Public Health; Boston University CTE Center (A.C.M.), Boston University Alzheimer's Disease Center, Departments of Neurology and Pathology & Laboratory Medicine, Boston University School of Medicine; VA Boston Healthcare System (A.C.M.), US Department of Veteran Affairs, MA; Psychiatry Neuroimaging Laboratory (M.E.S.), Departments of Psychiatry and Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Chambers-Grundy Center for Transformative Neuroscience (J.L.C.), Department of Brain Health, University of Nevada School of Integrated Health Sciences; Cleveland Clinic Lou Ruvo Center for Brain Health (J.L.C.), Las Vegas, NV; Banner Alzheimer's Institute (E.M.R.), Arizona State University; Department of Psychiatry (E.M.R.), University of Arizona, Phoenix, AZ; and Boston University CTE Center (R.A.S.), Boston University Alzheimer's Disease Center, Departments of Neurology, Neurosurgery, and Anatomy & Neurobiology, Boston University School of Medicine, MA. bobstern@bu.edu.
Abstract
OBJECTIVE: To develop evidence-informed, expert consensus research diagnostic criteria for traumatic encephalopathy syndrome (TES), the clinical disorder associated with neuropathologically diagnosed chronic traumatic encephalopathy (CTE). METHODS: A panel of 20 expert clinician-scientists in neurology, neuropsychology, psychiatry, neurosurgery, and physical medicine and rehabilitation, from 11 academic institutions, participated in a modified Delphi procedure to achieve consensus, initiated at the First National Institute of Neurological Disorders and Stroke Consensus Workshop to Define the Diagnostic Criteria for TES, April, 2019. Before consensus, panelists reviewed evidence from all published cases of CTE with neuropathologic confirmation, and they examined the predictive validity data on clinical features in relation to CTE pathology from a large clinicopathologic study (n = 298). RESULTS: Consensus was achieved in 4 rounds of the Delphi procedure. Diagnosis of TES requires (1) substantial exposure to repetitive head impacts (RHIs) from contact sports, military service, or other causes; (2) core clinical features of cognitive impairment (in episodic memory and/or executive functioning) and/or neurobehavioral dysregulation; (3) a progressive course; and (4) that the clinical features are not fully accounted for by any other neurologic, psychiatric, or medical conditions. For those meeting criteria for TES, functional dependence is graded on 5 levels, ranging from independent to severe dementia. A provisional level of certainty for CTE pathology is determined based on specific RHI exposure thresholds, core clinical features, functional status, and additional supportive features, including delayed onset, motor signs, and psychiatric features. CONCLUSIONS: New consensus diagnostic criteria for TES were developed with a primary goal of facilitating future CTE research. These criteria will be revised as updated clinical and pathologic information and in vivo biomarkers become available.
OBJECTIVE: To develop evidence-informed, expert consensus research diagnostic criteria for traumatic encephalopathy syndrome (TES), the clinical disorder associated with neuropathologically diagnosed chronic traumatic encephalopathy (CTE). METHODS: A panel of 20 expert clinician-scientists in neurology, neuropsychology, psychiatry, neurosurgery, and physical medicine and rehabilitation, from 11 academic institutions, participated in a modified Delphi procedure to achieve consensus, initiated at the First National Institute of Neurological Disorders and Stroke Consensus Workshop to Define the Diagnostic Criteria for TES, April, 2019. Before consensus, panelists reviewed evidence from all published cases of CTE with neuropathologic confirmation, and they examined the predictive validity data on clinical features in relation to CTE pathology from a large clinicopathologic study (n = 298). RESULTS: Consensus was achieved in 4 rounds of the Delphi procedure. Diagnosis of TES requires (1) substantial exposure to repetitive head impacts (RHIs) from contact sports, military service, or other causes; (2) core clinical features of cognitive impairment (in episodic memory and/or executive functioning) and/or neurobehavioral dysregulation; (3) a progressive course; and (4) that the clinical features are not fully accounted for by any other neurologic, psychiatric, or medical conditions. For those meeting criteria for TES, functional dependence is graded on 5 levels, ranging from independent to severe dementia. A provisional level of certainty for CTE pathology is determined based on specific RHI exposure thresholds, core clinical features, functional status, and additional supportive features, including delayed onset, motor signs, and psychiatric features. CONCLUSIONS: New consensus diagnostic criteria for TES were developed with a primary goal of facilitating future CTE research. These criteria will be revised as updated clinical and pathologic information and in vivo biomarkers become available.
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