An unusual autopsy case of progressive muscular atrophy with widespread fus positive inclusions

Abstract

Progressive muscular atrophy (PMA) is the lower motor neuron-predominant form of motor neuron disease (MND). MND is a relatively common, progressive fatal neurodegenerative disease, the pathogenetic basis of which is not fully understood. Recent genetic studies have identified mutations in the Fused in sarcoma/ translated in liposarcoma (FUS/TLS) gene at chromosome 16 in approximately 3% of familial MND and less than 1% of sporadic patients. The mutation usually leads to an earlier onset and more aggressive phenotype of MND. In this case study we describe the autopsy neuropathology of a late-onset and seemingly sporadic case of PMA. The pathology was dominated by loss of lower motor neurons and widespread FUS positive cytoplasmic inclusions. These inclusions were negative for TDP-43, distinguishing them from typical sporadic MND cases. FUS positive cytoplasmic inclusions were also found in other regions, in both neurons and glia. They were present in brainstem nuclei, cerebellum and deep grey structures but were absent from hippocampus and neocortical areas. This unique case broadens the phenotypic and neuropatho-logical spectrum of FUS-related neurodegenerative conditions and may provide additional insights into the role of FUS in both sporadic and familial MND.