Evaluation of the specificity of the central diagnostic criterion for chronic traumatic encephalopathy.

INTRODUCTION: Chronic traumatic encephalopathy (CTE) is a postmortem diagnosis. Consensus postmortem, but not antemortem, diagnostic criteria have been established. A key factor in these criteria is evidence of phosphorylated-tau (p-tau) around sulcal vessels in the cortex. However, this sign has been observed anecdotally in a diverse range of neurodegenerative diseases (NDD). We therefore hypothesise that this criterion may lack specificity.
METHODS: To test this, we assessed patients with NDD, but no documented history of brain trauma, for sulcal p-tau. Tissue was retrieved from Dublin Brain Bank (known NDD n = 17; control with no diagnosed NDD n = 6; CTE n = 1), and slides were prepared from three sites with a predilection for trauma: superior frontal gyrus, temporal pole, and superior temporal gyrus. We stained the resulting anonymised slides with both hemotoxylin and eosin (H&E) and p-tau. Three neuropathologists, blinded to the clinical history and neuropathological diagnosis in each instance, evaluated each case for sulcal p-tau. We calculated the interrater agreement, using Fleiss's kappa, and the specificity of this neuropathological sign.
RESULTS: Sulcal p-tau was highly specific to diagnosed CTE cases (specificity 0.98), with moderate interrater agreement (κ = 0.45).
CONCLUSION: In conclusion, therefore, we observed sulcal p-tau to be a sign highly specific to CTE when compared with NDD cases in the absence of head trauma.