Volume Loss in the Mammillary Bodies, Fornix, and Other Papez Circuit Structures in Fighters with Traumatic Encephalopathy Syndrome.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disorder that can only be diagnosed on autopsy. Traumatic encephalopathy syndrome (TES) is a proposed diagnostic framework for the clinical syndrome of CTE that is based on patient history and clinical examination. Given that mammillary body and fornix volume loss has been demonstrated in CTE and is measurable on MRI, this study aims to investigate the relationship between TES status and in vivo mammillary body and fornix volumes to support the role of these structures as imaging biomarkers for TES. Additionally, associations with other structures of the Papez circuit and relevant cognitive tests were explored. This observational cohort study used data from a subset of fighters and control participants in the Professional Athletes Brain Health Study (PABHS). The relationship was examined between clinical groups (controls, TES-negative fighters, and TES-positive fighters) and automated measurements of mammillary body and fornix size. Manual measurements were also performed to confirm the automated results and demonstrate clinical relevance. Associations were assessed between mammillary body/fornix size, cognitive scores, and volumes of other structures including components of the Papez circuit. The sample consisted of 177 individuals (61 controls, 46 TES-positive fighters, and 70 TES-negative fighters). Automated measurements of mammillary body volumes were on average ∼7.6 mm³ (15%) smaller in TES-positive fighters than in TES-negative fighters and controls (p < 0.001 for both). Automated measurements of fornix volumes were on average 110.5 mm³ (24%) smaller in TES-positive fighters than in TES-negative fighters and 156.5 mm³ (29%) smaller in TES-positive fighters than in controls (p < 0.001 for both). Similar findings were observed with manual measurements. Decreased mammillary body and fornix size were associated with lower volumes in the other components of the Papez circuit/associated structures (p < 0.01 for all) and worse psychomotor (p = 0.001 for both) and memory (p < 0.001 for both) scores. This decrease in mammillary body and fornix size among TES-positive fighters suggests that increased exposure to repetitive head impacts damages these structures, and that imaging assessment of the mammillary bodies and fornix is a feasible biomarker to support the diagnosis of TES.