Dementia After Moderate-Severe Traumatic Brain Injury: Coexistence of Multiple Proteinopathies
Dementia After Moderate-Severe Traumatic Brain Injury: Coexistence of Multiple Proteinopathies
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DOI：
10.1093/jnen/nlx101
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发表时间：
2018-01-01
影响因子：
3.2
通讯作者：
Perl, Daniel P.
中科院分区：
文献类型：
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作者：
Kenney, Kimbra;Iacono, Diego;Perl, Daniel P.
我们报告了 2 名中重度创伤性脑损伤 (TBI) 后出现早发性痴呆患者的临床、神经影像学和神经病理学特征。神经病理学评估显示，两例病例均存在丰富的β-淀粉样蛋白神经炎和核心斑块、弥漫性β-淀粉样蛋白斑块以及频繁的过度磷酸化tau神经原纤维缠结（NFT），涉及大部分皮质，包括岛叶和乳头体。病例1还显示浅层和深层皮质层都有NFT，偶尔有血管周围和脑沟深度NFT，以及顶叶白质稀疏，这与离体MRI观察到的顶叶纤维束减少相对应。病例2还显示NFT在皮质、下丘脑和脑干的浅层占主导地位，皮质、杏仁核和脑干中弥漫性路易体，以及神经元内TDP-43包涵体。神经病理学诊断为以慢性创伤性脑病和白质缺失为特征的非典型阿尔茨海默病 (AD)（病例 1），以及非典型 AD、路易体痴呆和共存 TDP-43 病理学（病例 2）。这些发现支持 TBI 和痴呆之间的流行病学关联，并进一步描述了 TBI 后可能积累的各种错误折叠蛋白的特征。需要对全面的临床、影像、遗传和神经病理学数据进行分析，以描述与中重度 TBI 后发生的痴呆相关的完整临床病理学谱。
We report the clinical, neuroimaging, and neuropathologic characteristics of 2 patients who developed early onset dementia after a moderate-severe traumatic brain injury (TBI). Neuropathological evaluation revealed abundant beta-amyloid neuritic and cored plaques, diffuse beta-amyloid plaques, and frequent hyperphosphorylated-tau neurofibrillary tangles (NFT) involving much of the cortex, including insula and mammillary bodies in both cases. Case 1 additionally showed NFTs in both the superficial and deep cortical layers, occasional perivascular and depth-of-sulci NFTs, and parietal white matter rarefaction, which corresponded with decreased parietal fiber tracts observed on ex vivo MRI. Case 2 additionally showed NFT predominance in the superficial layers of the cortex, hypothalamus and brainstem, diffuse Lewy bodies in the cortex, amygdala and brainstem, and intraneuronal TDP-43 inclusions. The neuropathologic diagnoses were atypical Alzheimer disease (AD) with features of chronic traumatic encephalopathy and white matter loss (Case 1), and atypical AD, dementia with Lewy bodies and coexistent TDP-43 pathology (Case 2). These findings support an epidemiological association between TBI and dementia and further characterize the variety of misfolded proteins that may accumulate after TBI. Analyses with comprehensive clinical, imaging, genetic, and neuropathological data are required to characterize the full clinicopathological spectrum associated with dementias occurring aftermoderate-severe TBI.