Clinical Manifestations.

Area of Science:

• Neuropathology
• Neuroscience
• Clinical Neurology

Background:

• The validity of the 2021 National Institute of Neurological Disorders and Stroke (NINDS) Traumatic Encephalopathy Syndrome (TES) criteria for diagnosing chronic traumatic encephalopathy (CTE) in living individuals has not been previously assessed.
• Assessing these criteria is crucial for advancing CTE diagnosis and patient care.

Purpose of the Study:

• To evaluate the diagnostic accuracy of the 2021 NINDS TES criteria in a cohort of brain donors with varying repetitive head impact (RHI) and traumatic brain injury (TBI) exposures.
• To determine the sensitivity, specificity, and likelihood ratios of the TES criteria compared to neuropathological findings of CTE.

Main Methods:

• Brain donors from 6 brain banks and 9 RHI/TBI exposure groups were selected, along with 5 age groups.
• Neuropathologists blinded to clinical data applied NINDS/NIBIB CTE neuropathological criteria and staging (I-IV).
• Clinicians blinded to neuropathological data adjudicated TES diagnoses (suggestive, possible, probable) using informant interviews and medical records.

Main Results:

• Among 193 brain donors, 29.5% met clinical criteria for TES (possible/probable CTE) and 21.8% met neuropathological criteria for CTE stages II-IV.
• Overall TES criteria sensitivity was 0.79 and specificity was 0.84, with higher accuracy in individuals aged 50 and older (sensitivity 0.93, specificity 0.90).
• False positives included Stage I CTE and other neurodegenerative diseases; false negatives had suggestive CTE, alternative etiologies, or inconclusive courses.

Conclusions:

• The 2021 TES criteria demonstrate good sensitivity and specificity for identifying CTE pathology across diverse RHI/TBI exposures.
• The criteria are particularly effective in individuals over age 50, suggesting their potential utility in clinical settings.
• These findings support the optimism for using the 2021 TES criteria in the clinical diagnosis of CTE.