军人长程肌萎缩性侧索硬化症的神经病理学特征。
Neuropathological profile of long-duration amyotrophic lateral sclerosis in military Veterans.
机构信息
VA Boston Healthcare System, Boston, MA.
Southern Arizona VA Healthcare System, Tucson, AZ.
出版信息
Brain Pathol. 2020 Nov;30(6):1028-1040. doi: 10.1111/bpa.12876. Epub 2020 Aug 4.
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting both the upper and lower motor neurons. Although ALS typically leads to death within 3 to 5 years after initial symptom onset, approximately 10% of patients with ALS live more than 10 years after symptom onset. We set out to determine similarities and differences in clinical presentation and neuropathology in persons with ALS with long vs. those with standard duration. Participants were United States military Veterans with a pathologically confirmed diagnosis of ALS (n = 179), dichotomized into standard duration (<10 years) and long-duration (≥10 years). The ALS Functional Rating Scale-Revised (ALSFRS-R) was administered at study entry and semi-annually thereafter until death. Microglial density was determined in a subset of participants. long-duration ALS occurred in 76 participants (42%) with a mean disease duration of 16.3 years (min/max = 10.1/42.2). Participants with long-duration ALS were younger at disease onset (P = 0.002), had a slower initial ALS symptom progression on the ALSFRS-R (P < 0.001) and took longer to diagnose (P < 0.002) than standard duration ALS. Pathologically, long-duration ALS was associated with less frequent TDP-43 pathology (P < 0.001). Upper motor neuron degeneration was similar; however, long-duration ALS participants had less severe lower motor neuron degeneration at death (P < 0.001). In addition, the density of microglia was decreased in the corticospinal tract (P = 0.017) and spinal cord anterior horn (P = 0.009) in long-duration ALS. Notably, many neuropathological markers of ALS were similar between the standard and long-duration groups and there was no difference in the frequency of known ALS genetic mutations. These findings suggest that the lower motor neuron system is relatively spared in long-duration ALS and that pathological progression is likely slowed by as yet unknown genetic and environmental modifiers.
肌萎缩侧索硬化症（ALS）是一种进行性神经退行性疾病，影响上下运动神经元。尽管 ALS 通常在初始症状出现后 3 至 5 年内导致死亡，但大约 10%的 ALS 患者在症状出现后超过 10 年仍存活。我们旨在确定具有长病程和标准病程的 ALS 患者在临床表现和神经病理学方面的异同。参与者为美国退伍军人，其病理确诊为 ALS（n=179），分为标准病程（<10 年）和长病程（≥10 年）。在研究开始时进行 ALS 功能评定量表修订版（ALSFRS-R）评估，此后每半年评估一次，直至死亡。在一部分参与者中测定小胶质细胞密度。长病程 ALS 发生在 76 名参与者（42%）中，平均病程为 16.3 年（最小/最大=10.1/42.2）。长病程 ALS 患者发病年龄较小（P=0.002），ALSFRS-R 上初始 ALS 症状进展较慢（P<0.001），诊断时间较长（P<0.002）。病理上，长病程 ALS 与 TDP-43 病理较少有关（P<0.001）。上运动神经元变性相似；然而，长病程 ALS 患者在死亡时下运动神经元变性较轻（P<0.001）。此外，长病程 ALS 患者皮质脊髓束（P=0.017）和脊髓前角（P=0.009）中的小胶质细胞密度降低。值得注意的是，标准病程和长病程组的许多 ALS 神经病理学标志物相似，并且已知 ALS 基因突变的频率没有差异。这些发现表明，长病程 ALS 中较低的运动神经元系统相对较少受累，并且病理进展可能由于未知的遗传和环境修饰因子而减缓。
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