Department of Medical Pathology and Laboratory Medicine, School of Medicine, University of California, Davis, Sacramento, California.
Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, The David Geffen School of Medicine, University of California, Los Angeles, California.
Neurosurgery. 2018 Feb 1;82(2):237-246. doi: 10.1093/neuros/nyx536.
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.
目前,只能对活着的患者做出慢性创伤性脑病(CTE)的推测性诊断。我们提出了一种方法,该方法可能有助于对一名患有 CTE 的美式足球运动员的脑尸检确认[F-18]FDDNP-PET 发现的 CTE 进行明确诊断。[F-18]FDDNP-PET 成像在研究对象死亡前 52 个月进行。确定了皮质和皮质下感兴趣区域的相对分布容积参数图像和结合值。死后,检查大脑以确定神经退行性变化的拓扑分布。使用 Spearman 等级相关系数进行神经病理学与[F-18]FDDNP-PET 结合模式之间的相关性。情绪、行为、运动和认知变化与慢性创伤性脑脊髓病一致,终生有 22 年接触美式足球的风险。大脑中存在 tau、淀粉样蛋白和 TDP-43 神经病理学底物,具有不同的拓扑选择性分布。[F-18]FDDNP-PET 结合水平与脑 tau 沉积相关(rs = 0.59,P =.02),大脑矢状旁区和脑室旁区以及脑干的相对分布体积最高。未观察到与淀粉样蛋白或 TDP-43 沉积相关。[F-18]FDDNP-PET 信号可能与 CTE 中的 tau 沉积的神经病理学模式一致,涉及到美式足球运动员承受最大剪切、角旋转加速度减速力的区域,这与 CTE 的独特和不同的拓扑脆弱性和选择性一致,也涉及中脑和边缘区域。需要进一步的研究来确定不同和选择性的[F-18]FDDNP-PET 是否可用于对高危患者的 CTE 进行诊断。