The spectrum of disease in chronic traumatic encephalopathy
The spectrum of disease in chronic traumatic encephalopathy
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DOI：
10.1093/brain/aws307
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发表时间：
2013-01-01
期刊：
影响因子：
14.5
通讯作者：
Cantu, Robert C.
中科院分区：
文献类型：
--
作者：
McKee, Ann C.;Stein, Thor D.;Cantu, Robert C.
慢性创伤性脑病是一种进行性脑病，发生作为重复性轻度创伤性脑损伤的后果。我们分析了85名有重复性轻度创伤性脑损伤史的受试者的死后大脑，并在68名受试者中发现了慢性创伤性脑病的证据：所有受试者均为男性，年龄从17岁到98岁（平均59.5岁），包括64名运动员，21名退伍军人（其中86%也是运动员）和1名从事自残头部撞击行为的个体。18名年龄和性别匹配的无重复性轻度创伤性脑损伤史的个体作为对照组。在慢性创伤性脑病中，过度磷酸化的tau病理范围从额叶新皮质的局灶性血管周围中心神经原纤维缠结到影响广泛脑区（包括内侧颞叶）的严重tau病变，从而允许从I-IV期逐步分期病理。在慢性创伤性脑病的所有阶段，在皮层深部和皮层下白质中发现多灶性轴索静脉曲张和轴索丧失。在85%的病例中也发现了TAR dna结合蛋白43免疫反应性包涵体和神经突，范围从局灶性病理的I- iii期到广泛的包涵体和神经突的IV期。I期慢性创伤性脑病的症状包括头痛、注意力和注意力丧失。II期的附加症状包括抑郁、爆发力和短期记忆丧失。在第三阶段，发现执行功能障碍和认知障碍，在第四阶段，痴呆，找字困难和攻击为特征。有34名美国橄榄球运动员的运动暴露数据；慢性创伤性脑病的阶段与足球比赛时间的延长、足球后的存活率和死亡年龄相关。慢性创伤性脑病是43例（63%）的唯一诊断；8人还被诊断患有运动神经元疾病（12%），7人患有阿尔茨海默病（11%），11人患有路易体病（16%），4人患有额颞叶变性（6%）。在慢性外伤性脑病中，伴随广泛的轴突破坏和丧失的神经系统中，有一个有序和可预测的过度磷酸化tau异常的进展。慢性创伤性脑病与其他神经退行性疾病的频繁关联表明，重复性脑损伤和过度磷酸化的tau蛋白沉积促进了其他异常聚集蛋白的积累，包括TAR dna结合蛋白43、淀粉样蛋白β和α -突触核蛋白。
Chronic traumatic encephalopathy is a progressive tauopathy that occurs as a consequence of repetitive mild traumatic brain injury. We analysed post-mortem brains obtained from a cohort of 85 subjects with histories of repetitive mild traumatic brain injury and found evidence of chronic traumatic encephalopathy in 68 subjects: all males, ranging in age from 17 to 98 years (mean 59.5 years), including 64 athletes, 21 military veterans (86% of whom were also athletes) and one individual who engaged in self-injurious head banging behaviour. Eighteen age- and gender-matched individuals without a history of repetitive mild traumatic brain injury served as control subjects. In chronic traumatic encephalopathy, the spectrum of hyperphosphorylated tau pathology ranged in severity from focal perivascular epicentres of neurofibrillary tangles in the frontal neocortex to severe tauopathy affecting widespread brain regions, including the medial temporal lobe, thereby allowing a progressive staging of pathology from stages I-IV. Multifocal axonal varicosities and axonal loss were found in deep cortex and subcortical white matter at all stages of chronic traumatic encephalopathy. TAR DNA-binding protein 43 immunoreactive inclusions and neurites were also found in 85% of cases, ranging from focal pathology in stages I-III to widespread inclusions and neurites in stage IV. Symptoms in stage I chronic traumatic encephalopathy included headache and loss of attention and concentration. Additional symptoms in stage II included depression, explosivity and short-term memory loss. In stage III, executive dysfunction and cognitive impairment were found, and in stage IV, dementia, word-finding difficulty and aggression were characteristic. Data on athletic exposure were available for 34 American football players; the stage of chronic traumatic encephalopathy correlated with increased duration of football play, survival after football and age at death. Chronic traumatic encephalopathy was the sole diagnosis in 43 cases (63%); eight were also diagnosed with motor neuron disease (12%), seven with Alzheimer's disease (11%), 11 with Lewy body disease (16%) and four with frontotemporal lobar degeneration (6%). There is an ordered and predictable progression of hyperphosphorylated tau abnormalities through the nervous system in chronic traumatic encephalopathy that occurs in conjunction with widespread axonal disruption and loss. The frequent association of chronic traumatic encephalopathy with other neurodegenerative disorders suggests that repetitive brain trauma and hyperphosphorylated tau protein deposition promote the accumulation of other abnormally aggregated proteins including TAR DNA-binding protein 43, amyloid beta protein and alpha-synuclein.