Abstract
Previous post-mortem epilepsy series showed phosphorylated tau (pTau) accumulation in relation to traumatic brain injury (TBI) rather than driven by seizure frequency. The Corsellis Epilepsy Collection, established in the mid-20th century, represents brain samples collected from patients living with a range of epilepsies from the 1880s to 1990s. Our aim was to interrogate this historical archive to explore relationships between epilepsy, trauma and tau pathology. AT8 immunohistochemistry for pTau was carried out in 102 cases (55% male, with mean age at death of 62 years) on frontal, temporal, amygdala, hippocampal and lesional cortical regions and evaluated using current NINDS criteria for chronic traumatic encephalopathy (CTE) and Braak staging with beta-amyloid, AT8-GFAP and other pTau markers (CP13, PHF1, AT100, AT180) in selected cases. CTE-neuropathologic change (CTE-NC) was identified in 15.7% and was associated with the presence of astroglial tau, a younger age of onset of epilepsy, evidence of TBI and institutionalisation for epilepsy compared to cases without CTE-NC, but not for seizure type or frequency. Memory impairment was noted in 43% of cases with CTE-NC, and a significantly younger age of death; more frequent reports of sudden and unexpected death (p <0.05-0.001) were noted in cases with CTE-NC. In contrast, a higher Braak stage was associated with late-onset epilepsy and cognitive decline. Of note, 9% of cases showed no pTau, including cases with long epilepsy duration, poor seizure control and a history of prior TBI. In summary, this cohort includes patients with more severe and diverse forms of epilepsy, with CTE-NC observed more frequently than reported in non-epilepsy community-based studies (0%-8%) but lower than published series from contact sports participants (32%-87%). Although the literature does not report increased epilepsy occurring in CTE syndrome, our findings support an increased risk of CTE in epilepsy syndromes, likely primarily related to increased TBI.