Department of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California, USA.
Program for Neurotrauma, Neuroproteomics & Biomarkers Research, Department of Emergency Medicine, Neuroscience, Psychiatry and Chemistry, McKnight Brain Institute, University of Florida, Gainesville, Florida, USA.
J Neurotrauma. 2022 Sep;39(17-18):1195-1213. doi: 10.1089/neu.2022.0060. Epub 2022 Jun 6.
Traumatic encephalopathy syndrome (TES) criteria were developed to aid diagnosis of chronic traumatic encephalopathy (CTE) pathology during life. Interpreting clinical and biomarker findings in patients with TES during life necessitates autopsy-based determination of the neuropathological profile. We report a clinicopathological series of nine patients with previous repetitive head impacts (RHI) classified retrospectively using the recent TES research framework (100% male and white/Caucasian, age at death 49-84) who completed antemortem neuropsychological evaluations, T1-weighted magnetic resonance imaging, diffusion tensor imaging ( = 6), (18)F-fluorodeoxyglucose-positron emission tomography ( = 5), and plasma measurement of neurofilament light (NfL), glial fibrillary acidic protein (GFAP), and total tau ( = 8). Autopsies were performed on all patients. Cognitively, low test scores and longitudinal decline were relatively consistent for memory and executive function. Medial temporal lobe atrophy was observed in all nine patients. Poor white matter integrity was consistently found in the fornix. Glucose hypometabolism was most common in the medial temporal lobe and thalamus. Most patients had elevated plasma GFAP, NfL, and total tau at their initial visit and a subset showed longitudinally increasing concentrations. Neuropathologically, five of the nine patients had CTE pathology ( = 4 "High CTE"/McKee Stage III-IV, = 1 "Low CTE"/McKee Stage I). Primary neuropathological diagnoses (i.e., the disease considered most responsible for observed symptoms) were frontotemporal lobar degeneration ( = 2 FTLD-TDP, = 1 FTLD-tau), Alzheimer disease ( = 3), CTE ( = 2), and primary age-related tauopathy ( = 1). In addition, hippocampal sclerosis was a common neuropathological comorbidity ( = 5) and associated with limbic-predominant TDP-43 proteinopathy ( = 4) or FTLD-TDP ( = 1). Memory and executive function decline, limbic system brain changes (atrophy, decreased white matter integrity, hypometabolism), and plasma biomarker alterations are common in RHI and TES but may reflect multiple neuropathologies. In particular, the neuropathological differential for patients with RHI or TES presenting with medial temporal atrophy and memory loss should include limbic TDP-43. Researchers and clinicians should be cautious in attributing cognitive, neuroimaging, or other biomarker changes solely to CTE tau pathology based on previous RHI or a TES diagnosis alone.
创伤性脑病综合征（TES）标准的制定是为了在生前协助诊断慢性创伤性脑病（CTE）的病理变化。在生前解释 TES 患者的临床和生物标志物发现，需要通过尸检确定神经病理学特征。我们报告了一个临床病理系列，其中包括 9 名以前有过重复性头部冲击（RHI）的患者，这些患者使用最近的 TES 研究框架进行回顾性分类（100%为男性和白种人/高加索人，死亡年龄 49-84 岁），他们完成了生前神经心理学评估、T1 加权磁共振成像、弥散张量成像（ = 6）、（18）F-氟脱氧葡萄糖正电子发射断层扫描（ = 5）和神经丝轻链（NfL）、神经胶质纤维酸性蛋白（GFAP）和总 tau（ = 8）的血浆测量。所有患者均进行了尸检。认知方面，记忆和执行功能的测试分数较低和纵向下降相对一致。所有 9 名患者的内侧颞叶均有萎缩。穹窿的白质完整性较差。葡萄糖代谢低下最常见于内侧颞叶和丘脑。大多数患者在首次就诊时的血浆 GFAP、NfL 和总 tau 升高，部分患者表现出纵向升高的浓度。神经病理学上，9 名患者中有 5 名（ = 4 名“高 CTE”/McKee Ⅲ-Ⅳ期， = 1 名“低 CTE”/McKee Ⅰ期）患有 CTE 病理学。主要的神经病理学诊断（即，最有可能导致观察到的症状的疾病）为额颞叶变性（ = 2 例 FTLD-TDP， = 1 例 FTLD-tau）、阿尔茨海默病（ = 3 例）、CTE（ = 2 例）和原发性年龄相关性 tau 病（ = 1 例）。此外，海马硬化是一种常见的神经病理学合并症（ = 5），与边缘系统为主的 TDP-43 蛋白病（ = 4）或 FTLD-TDP（ = 1）相关。RHI 和 TES 患者的记忆和执行功能下降、边缘系统脑改变（萎缩、白质完整性降低、代谢降低）以及血浆生物标志物改变较为常见，但可能反映出多种神经病理学变化。特别是，对于以内侧颞叶萎缩和记忆丧失为表现的 RHI 或 TES 患者，其神经病理学鉴别诊断应包括边缘系统 TDP-43。基于以前的 RHI 或 TES 诊断，研究人员和临床医生应谨慎将认知、神经影像学或其他生物标志物变化仅归因于 CTE tau 病理学。
