Embracing the Unknown in the Diagnosis of Traumatic Encephalopathy Syndrome

Repeated head injuries (RHIs) are associated with chronic traumatic encephalopathy (CTE), diagnosed neuropathologically by the presence of hyperphosphorylated tau (p-tau) in a pattern defined in the 2016 diagnostic criteria.¹ In this issue of Neurology®, Katz et al.² have presented National Institute of Neurological Disorders and Stroke consensus diagnostic criteria for traumatic encephalopathy syndrome (TES), the clinical syndrome associated with CTE, for use in research. A consensus panel of 20 clinician-staff scientists reviewed 40 studies (229 cases) reporting neuropathologically diagnosed CTE and clinical features and underwent 4 rounds of a modified Delphi procedure to reach consensus. The proposed criteria for TES diagnosis are (1) substantial exposure to RHIs; (2) core clinical features, specifically cognitive impairment (involving episodic memory or executive dysfunction), neurobehavioral dysregulation (explosiveness, impulsivity, rage, violent outbursts, emotional lability), or both; and (3) not fully accounted for by other disorders, although the presence of another neurodegenerative disease, substance use disorder, posttraumatic stress disorder, or mood/anxiety disorders does not exclude TES. If an individual fulfills all 3 criteria, that individual is then assessed for level of functional dependence/dementia under the following levels: independent, subtle/mild functional limitation, mild dementia, moderate dementia, or severe dementia. Katz et al. further suggest criteria for assigning provisional levels of certainty for CTE pathology from a TES diagnosis (suggestive, possible, probable, or definite) based on TES criteria and a set of supportive features including delayed onset of symptoms, motor signs (parkinsonism, dysarthria, ataxia, and imbalance), and psychiatric features. Individuals with no history of contact sports can only meet the criteria for suggestive of CTE. If an individual meets the criteria for TES, has had substantial (≥5 years) or extensive (≥11 years) exposure to collisions in contact sports, and meets at least 2 supportive features, that individual is assigned possible or probable CTE. Definite CTE requires postmortem neuropathologic diagnosis.