The Second NINDS/NIBIB Consensus Meeting to Define Neuropathological Criteria for the Diagnosis of Chronic Traumatic Encephalopathy

J Neuropathol Exp Neurol. 2021 Feb 22;80(3):210-219. doi: 10.1093/jnen/nlab001.


Chronic traumatic encephalopathy (CTE) is a neurodegenerative disorder associated with exposure to head trauma. In 2015, a panel of neuropathologists funded by the NINDS/NIBIB defined preliminary consensus neuropathological criteria for CTE, including the pathognomonic lesion of CTE as "an accumulation of abnormal hyperphosphorylated tau (p-tau) in neurons and astroglia distributed around small blood vessels at the depths of cortical sulci and in an irregular pattern," based on review of 25 tauopathy cases. In 2016, the consensus panel met again to review and refine the preliminary criteria, with consideration around the minimum threshold for diagnosis and the reproducibility of a proposed pathological staging scheme. Eight neuropathologists evaluated 27 cases of tauopathies (17 CTE cases), blinded to clinical and demographic information. Generalized estimating equation analyses showed a statistically significant association between the raters and CTE diagnosis for both the blinded (OR = 72.11, 95% CI = 19.5-267.0) and unblinded rounds (OR = 256.91, 95% CI = 63.6-1558.6). Based on the challenges in assigning CTE stage, the panel proposed a working protocol including a minimum threshold for CTE diagnosis and an algorithm for the assessment of CTE severity as "Low CTE" or "High CTE" for use in future clinical, pathological, and molecular studies.

Keywords: Brain trauma; Chronic traumatic encephalopathy; Neurodegenerative disorders; Tauopathy; Traumatic brain injury.

Publication types

  • Consensus Development Conference, NIH
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Chronic Traumatic Encephalopathy / diagnosis
  • Chronic Traumatic Encephalopathy / pathology*
  • Female
  • Humans
  • Male
  • Middle Aged
  • National Institute of Biomedical Imaging and Bioengineering (U.S.) / standards*
  • National Institute of Neurological Disorders and Stroke (U.S.) / standards*
  • Neuropathology / methods
  • Neuropathology / standards*
  • Single-Blind Method
  • United States
  • Young Adult