Validity of Clinical Research Criteria for Chronic Traumatic Encephalopathy: The Understanding Neurologic Injury and Traumatic Encephalopathy (UNITE) Study (S39.004)

Background: Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease associated with repetitive head impacts (RHI). Currently, CTE only can be diagnosed post-mortem. Methods: We evaluated the brains of 73 deceased subjects with a history of RHI exposure from contact sports at the professional or collegiate levels or from active military service. Clinical data were collected through medical record review and retrospective structured and unstructured family interviews conducted by a behavioral neurologist or neuropsychologist. Blinded to the clinical data, a neuropathologist conducted a comprehensive assessment for neurodegenerative disease, including CTE, using published criteria. At a clinicopathological conference, a panel of physicians and neuropsychologists, blinded to the neuropathological data, reached a clinical consensus diagnosis using published criteria, including proposed clinical research criteria for CTE. Results: The clinical consensus panel diagnosed 63 subjects with possible or probable CTE. Fifty-seven subjects had a pathological diagnosis of CTE. The sensitivity and specificity of a diagnosis of possible or probable CTE for a pathological diagnosis of CTE was 0.95 and 0.44 respectively. Of the 9 false positives, 3 had other neurodegenerative disorders (AD, PSP, FTLD), 2 had significant vascular pathology and 4 had no significant neurodegenerative or vascular pathology. All 3 false negatives had mild behavioral symptoms that did not meet clinical research criteria. Two of 3 false negatives only had stage 1 CTE pathology. Conclusions: Clinical research criteria for CTE may be sensitive, but not specific for a pathological diagnosis of CTE. Future analyses will test the specificity of item-level symptoms to refine future iterations of the clinical criteria to improve their specificity. Disclosure: Dr. Mez has nothing to disclose. Dr. Solomon has nothing to disclose. Dr. Daneshvar has nothing to disclose. Dr. Montenigro has nothing to disclose. Dr. Kiernan has nothing to disclose. Dr. Murphy has nothing to disclose. Dr. Kriegel has nothing to disclose. Dr. Abdolmohamadi has nothing to disclose. Dr. Alosco has nothing to disclose. Dr. Stein has nothing to disclose. Dr. Goldstein has nothing to disclose. Dr. Katz has nothing to disclose. Dr. Kowall has nothing to disclose. Dr. Cantu has nothing to disclose. Dr. Stern has nothing to disclose. Dr. McKee has nothing to disclose.