Primary lateral sclerosis (PLS) is a controversial form of motor neuron disease (MND), with uncertainty whether it represents a distinct clinico-pathological entity or is simply a variant of classical amyotrophic lateral sclerosis (ALS). Neuropathological studies provide an opportunity to investigate these issues; however, there have been very few published descriptions of postmortem findings in clinically defined PLS, using modern techniques. Here, we report the neuropathological features of seven cases of PLS with age at onset ranging from 47 to 73 years and disease duration from 3.5 to 35 years. All cases showed chronic degeneration of the primary motor cortex and/or the corticospinal tracts with preservation of lower motor neurons (LMN). All five cases, in which motor cortex was available, had TDP-43 immunoreactive (TDP-ir) cortical pathology. In all seven cases, TDP-ir inclusions were also present in LMN; however, these were always rare, averaging less than one inclusion per tissue section. The finding of TDP-ir pathology in all our cases suggests that PLS and ALS are closely related conditions. Importantly however, the extremely minor involvement of LMN, even after very long disease duration in some cases, suggests that PLS is a distinct form of MND in which LMN are spared or protected.

原发性侧索硬化症 (PLS) 是运动神经元病 (MND) 的一种有争议的形式，不确定它是否代表一种独特的临床病理实体或仅仅是经典肌萎缩侧索硬化症 (ALS) 的一种变体。神经病理学研究为调查这些问题提供了机会；然而，使用现代技术对临床定义的 PLS 中的死后发现发表的描述很少。在这里，我们报告了 7 例 PLS 的神经病理学特征，发病年龄为 47 至 73 岁，病程为 3.5 至 35 年。所有病例均显示初级运动皮层和/或皮质脊髓束的慢性退化，同时保留下运动神经元 (LMN)。运动皮层可用的所有五例病例均具有 TDP-43 免疫反应性 (TDP-ir) 皮质病理学。在所有 7 个案例中，LMN 中也存在 TDP-ir 夹杂物；然而，这些总是很少见，每个组织切片平均少于一个夹杂物。在我们所有病例中发现 TDP-ir 病理学表明 PLS 和 ALS 是密切相关的疾病。然而重要的是，LMN 的极轻微参与，即使在某些情况下疾病持续时间很长，也表明 PLS 是一种独特的 MND 形式，其中 LMN 可以幸免或受到保护。