Chronic traumatic encephalopathy pathognomonic lesions occurring in isolation adjacent to infiltrative and non-infiltrative white matter lesions

Chronic traumatic encephalopathy (CTE) is defined by perivascular neuronal phosphorylated-tau accumulation at cortical sulcal depths. CTE has been mainly described in the context of repetitive, impact-type traumatic brain injury (rTBI), principally from contact sports. Rarely, CTE has been associated with single TBIs, including in relationship to healed leucotomy sites in brains from formerly institutionalized psychiatric patients without documented rTBI. Given that leucotomy principally involves severing of white matter, this could suggest involvement of axonal injury in CTE pathophysiology. We present three cases wherein isolated CTE pathology was identified adjacent to distinct white matter lesions. Case 1 is a 41-year-old man with history of hereditary hemorrhagic telangiectasia and resection of a cerebral arteriovenous malformation (AVM). Case 2 is a 46-year-old man with glioblastoma. Case 3 is a 52-year-old man with a remote cerebral infarct. Isolated CTE lesions were found adjacent to the aforementioned pathologies in each case. Additional CTE lesions were not identified despite extensive sampling. Multiple age-related tau astrogliopathy (ARTAG)-like lesions were also identified at other sulcal depths near the AVM resection site in Case 1. These cases may provide insights regarding the pathophysiology of the CTE pathognomonic lesion and the development of ARTAG-like pathology adjacent to long-standing mass lesions.