Amyotrophic lateral sclerosis of long clinical course clinically presenting with progressive muscular atrophy

Amyotrophic lateral sclerosis (ALS) primarily affects upper and lower motor neurons. Phosphorylated TAR DNA-binding protein of 43 kDa (TDP-43) inclusion bodies are reportedly a pathological hallmark of sporadic ALS. Here, we present an atypical case of sporadic ALS that progressed very slowly, persisted for 19 years, and clinically appeared to only affect the lower motor neurons; however, upper motor neuron degeneration was detected on autopsy. Furthermore, no inclusion bodies positive for phosphorylated TDP-43, ubiquitin, fused in sarcoma, or SOD1 were detected in the CNS. We performed exome-sequencing data analysis but found no genetic disorders. This was therefore an unusual case of lower motor neuron-predominant ALS without TDP-43 pathology or known gene-disease associations. We also reviewed autopsied ALS cases that progressed slowly and had no phosphorylated TDP-43 or ubiquitin positive inclusions and present the clinicopathological features of such cases. Based on these results, there may be a sporadic ALS subgroup that progresses slowly and shows 76 no accumulation of phosphorylated TDP-43.

This is the peer reviewed version of the following article: Matsubara, T. , Oda, M. , Takahashi, T. , Watanabe, C. , Tachiyama, Y. , Morino, H. , Kawakami, H. , Kaji, R. , Maruyama, H. , Murayama, S. and Izumi, Y. (2019), Amyotrophic lateral sclerosis of long clinical course clinically presenting with progressive muscular atrophy. Neuropathology, 39: 47-53, which has been published in final form at https://doi.org/10.1111/neup.12523. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.