Ito J, Shimizu H, Ohta K, et al. - In the present cohort study, the researchers sought to assess the clinicopathological characteristics of an unusual form of amyotrophic lateral sclerosis (ALS) with pallidonigroluysian degeneration (PNLD) and ascertain if ALS with PNLD serves a distinct ALS subtype. They picked those with PNLD from a cohort of 97 autopsied cases of sporadic ALS with phosphorylated 43kDa TAR DNA-binding protein (TDP-43) inclusions and examined their clinicopathological characteristics. Findings suggested that the PNL system may be involved in the ALS disease process, either nonselectively as part of multisystem degeneration, or selectively. ALS with selective involvement of PNL and motor systems shows unique clinicopathological characteristics and propagation routes of TDP-43, thus representing a distinct subtype of ALS.