Postmortem Autopsy-Confirmation of Antemortem [F-18]FDDNP-PET Scans in a Football Player With Chronic Traumatic Encephalopathy

Abstract

Currently, only presumptive diagnosis of chronic traumatic encephalopathy (CTE) can be made in living patients. We present a modality that may be instrumental to the definitive diagnosis of CTE in living patients based on brain autopsy confirmation of [F-18]FDDNP-PET findings in an American football player with CTE. [F-18]FDDNP-PET imaging was performed 52 mo before the subject's death. Relative distribution volume parametric images and binding values were determined for cortical and subcortical regions of interest. Upon death, the brain was examined to identify the topographic distribution of neurodegenerative changes. Correlation between neuropathology and [F-18]FDDNP-PET binding patterns was performed using Spearman rank-order correlation. Mood, behavioral, motor, and cognitive changes were consistent with chronic traumatic myeloencephalopathy with a 22-yr lifetime risk exposure to American football. There were tau, amyloid, and TDP-43 neuropathological substrates in the brain with a differential topographically selective distribution. [F-18]FDDNP-PET binding levels correlated with brain tau deposition (rs = 0.59, P = .02), with highest relative distribution volumes in the parasagittal and paraventricular regions of the brain and the brain stem. No correlation with amyloid or TDP-43 deposition was observed. [F-18]FDDNP-PET signals may be consistent with neuropathological patterns of tau deposition in CTE, involving areas that receive the maximal shearing, angular-rotational acceleration-deceleration forces in American football players, consistent with distinctive and differential topographic vulnerability and selectivity of CTE beyond brain cortices, also involving midbrain and limbic areas. Future studies are warranted to determine whether differential and selective [F-18]FDDNP-PET may be useful in establishing a diagnosis of CTE in at-risk patients.

Keywords: Antemortem; Autopsy; CTE; Football player; [F-18]FDDNP-PET.

Copyright © 2017 by the Congress of Neurological Surgeons.

Figures

FIGURE 1.

Bar chart illustrating the differential regional [F-18]FDDNP-PET DVR values with highest values noted in parasagittal and sagittal periventricular regions of the brain including the subcortical ganglia, amygdala, and midbrain. Note also the highest brain signals in the medial temporal and frontal lobes.

FIGURE 2.

Top panel: immunohistochemistry photomicrographs (×400) of parietal cortex, midbrain, amygdala, and hippocampus show the presence of tau neuropathological deposits in these regions. Bottom panel: representative transaxial (2 sections), sagittal (middle), and coronal sections (right) of [F-18]FDDNP-PET images with high signals in the periventricular subcortical regions, amygdala, and midbrain. Warmer colors (red and yellow) show areas with higher [F-18]FDDNP binding signals.

FIGURE 3.

Photomicrographs of tau, beta-A4, and TDP-43 immunostained sections of the brain and spinal medulla: A and B, neocortex showing differential densities of tau neuropathological substrates. A, Frontal cortex, ×200 magnification. B, Parietal cortex, ×400 magnification. C, D, and E, Tegmental midbrain at ×100 magnification (C), amygdala at ×200 magnification (D), and ventral midbrain at ×200 magnification (E) showing frequent neuronal and extra-neuronal tau neuropathological substrates. F and G, Neuronal and extra-neuronal glial and neuropil tau neuropathological substrates in the spinal medulla (×400 magnification). H, Neocortex showing diffuse and neuritic amyloid plaques (×100 magnification). I, Midbrain showing TDP-43 inclusions and neurites (×400 magnification).